{"id":451,"date":"2023-08-29T19:43:39","date_gmt":"2023-08-29T11:43:39","guid":{"rendered":"https:\/\/blog.ineuro.net\/?p=451"},"modified":"2023-09-08T13:26:13","modified_gmt":"2023-09-08T05:26:13","slug":"%e6%96%87%e7%8c%ae%e9%98%85%e8%af%bb%ef%bc%9a%e5%a2%9e%e5%bc%ba%e6%98%9f%e5%bd%a2%e8%83%b6%e8%b4%a8%e7%bb%86%e8%83%9e%e5%86%85%e7%9a%84%e5%86%85%e6%ba%90%e6%80%a7%e5%a4%a7%e9%ba%bb%e7%b4%a0%e4%bf%a1","status":"publish","type":"post","link":"https:\/\/blog.ineuro.net\/index.php\/2023\/08\/29\/451\/","title":{"rendered":"\u6587\u732e\u9605\u8bfb\uff1a\u589e\u5f3a\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u5185\u7684\u5185\u6e90\u6027\u5927\u9ebb\u7d20\u4fe1\u53f7\u53ef\u4fc3\u8fdb\u521b\u4f24\u6027\u8111\u635f\u4f24\u7684\u6062\u590d"},"content":{"rendered":"

Title: Enhancing endocannabinoid signalling in astrocytes promotes recovery from traumatic brain injury<\/p>\n

DOI: https:\/\/doi.org\/10.1093\/brain\/awab310<\/a><\/p>\n

\u521b\u4f24\u6027\u8111\u635f\u4f24\u662f\u963f\u5c14\u8328\u6d77\u9ed8\u75c5\u548c\u75f4\u5446\u75c7\u53d1\u5c55\u7684\u4e00\u4e2a\u91cd\u8981\u98ce\u9669\u56e0\u7d20\u3002\u76ee\u524d\u8fd8\u6ca1\u6709\u6709\u6548\u7684\u9884\u9632\u548c\u6cbb\u7597\u521b\u4f24\u6027\u8111\u635f\u4f24\u5f15\u53d1\u7684\u7c7b\u4f3c\u963f\u5c14\u8328\u6d77\u9ed8\u75c5\u7684\u795e\u7ecf\u9000\u884c\u6027\u75be\u75c5\u7684\u7597\u6cd5\u3002\u836f\u7269\u6291\u5236\u5355\u9170\u7518\u6cb9\u8102\u9176\uff08\u4e00\u79cd\u964d\u89e3\u5185\u6e90\u5927\u9ebb\u7d202-\u82b1\u751f\u56db\u70ef\u9178\u7518\u6cb9\u916f\u7684\u5173\u952e\u9176\uff09\u53ef\u4ee5\u51cf\u8f7b\u521b\u4f24\u6027\u8111\u635f\u4f24\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u3002\u7136\u800c\uff0c\u5bfc\u81f4\u521b\u4f24\u6027\u8111\u635f\u4f24\u4e2d\u5355\u9170\u7518\u6cb9\u8102\u9176\u6291\u5236\u4ea7\u751f\u795e\u7ecf\u4fdd\u62a4\u4f5c\u7528\u7684\u673a\u5236\u5c1a\u4e0d\u6e05\u695a\u3002<\/p>\n

\u8be5\u7814\u7a76\u9996\u6b21\u5c55\u793a\u4e86\u5355\u9170\u7518\u6cb9\u8102\u9176\u57fa\u56e0\u6572\u9664\u51cf\u5c11\u4e86\u5c0f\u9f20\u5728\u53cd\u590d\u8f7b\u5ea6\u95ed\u5408\u5934\u90e8\u635f\u4f24\u66b4\u9732\u4e0b\u7684\u795e\u7ecf\u75c5\u7406\uff0c\u5e76\u907f\u514d\u4e86\u7a81\u89e6\u548c\u8ba4\u77e5\u4e0b\u964d\u3002\u8fd9\u4e9b\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\u4e3b\u8981\u662f\u7531\u4e8e\u6291\u5236\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-\u82b1\u751f\u56db\u70ef\u9178\u7518\u6cb9\u916f\u4ee3\u8c22\uff0c\u800c\u4e0d\u662f\u5728\u795e\u7ecf\u5143\u4e2d\u3002\u5355\u7ec6\u80deRNA\u6d4b\u5e8f\u6570\u636e\u663e\u793a\uff0c\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684\u5355\u9170\u7518\u6cb9\u8102\u9176\u6572\u9664\u5c0f\u9f20\u5728\u521b\u4f24\u6027\u8111\u635f\u4f24\u5f15\u53d1\u7684\u4e0e\u708e\u75c7\u6216\u8111\u5185\u7a33\u6001\u7ef4\u6301\u76f8\u5173\u7684\u57fa\u56e0\u8868\u8fbe\u53d8\u5316\u65b9\u9762\u8868\u73b0\u51fa\u66f4\u5f3a\u7684\u6297\u6027\uff0c\u8fd9\u5f71\u54cd\u4e86\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u548c\u5c0f\u80f6\u8d28\u7ec6\u80de\u3002\u901a\u8fc7\u5927\u9ebb\u7d20\u53d7\u4f53-1\u7684\u6572\u9664\u6216\u901a\u8fc7\u817a\u76f8\u5173\u75c5\u6bd2\u8f7d\u4f53\u4ecb\u5bfc\u7684\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u8fc7\u6c27\u5316\u7269\u9176\u4f53\u589e\u6b96\u6fc0\u6d3b\u53d7\u4f53-c\u7684\u6c89\u9ed8\uff0c\u5355\u9170\u7518\u6cb9\u8102\u9176\u706d\u6d3b\u4ea7\u751f\u7684\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\u88ab\u53d6\u6d88\u3002\u5728\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u8fc7\u8868\u8fbe\u8fc7\u6c27\u5316\u7269\u9176\u4f53\u589e\u6b96\u6fc0\u6d3b\u53d7\u4f53-c\u53ef\u4ee5\u9884\u9632\u521b\u4f24\u6027\u8111\u635f\u4f24\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u548c\u7a7a\u95f4\u5b66\u4e60\u548c\u8bb0\u5fc6\u969c\u788d\u3002<\/p>\n

\u4e00\u3001\u7814\u7a76\u80cc\u666f<\/h1>\n

\u5185\u6e90\u5927\u9ebb\u7d20\u7cfb\u7edf\u5305\u62ec\u5185\u6e90\u5927\u9ebb\u7d20\u3001\u5185\u6e90\u5927\u9ebb\u7d20\u53d7\u4f53\uff08CB1R\u548cCB2R\uff09\uff0c\u7531\u03949-\u56db\u6c22\u5927\u9ebb\u915a\uff0c\u5927\u9ebb\u7684\u4e3b\u8981\u7cbe\u795e\u6d3b\u6027\u6210\u5206\uff0c\u6240\u9776\u5411\u7684\u53d7\u4f53\u3001\u5408\u6210\u548c\u964d\u89e3\u5185\u6e90\u5927\u9ebb\u7d20\u7684\u9176\u4ee5\u53ca\u8f6c\u8fd0\u4f53\uff0c\u53c2\u4e0e\u4e86\u591a\u79cd\u751f\u7406\u3001\u836f\u7406\u548c\u75c5\u7406\u8fc7\u7a0b\u30022-\u82b1\u751f\u56db\u70ef\u9178\u7518\u6cb9\u916f\uff082-AG\uff09\u4e3b\u8981\u7531\u4e8c\u9170\u7518\u6cb9\u8102\u9176\uff08DAGLa\u548cDAGLb\uff09\u4ece\u4e8c\u9170\u7518\u6cb9\u5408\u6210\uff0c\u662f\u6700\u4e30\u5bcc\u7684\u5185\u6e90\u5927\u9ebb\u7d20\uff0c\u5bf9\u6297\u708e\u75c7\u5e76\u5728\u9762\u5bf9\u4fc3\u708e\u3001\u5174\u594b\u6bd2\u6027\u548c\u673a\u68b0\u6027\u4f24\u5bb3\u65f6\u5177\u6709\u795e\u7ecf\u4fdd\u62a4\u4f5c\u7528\u3002\u65e9\u671f\u7814\u7a76\u8868\u660e\uff0c2-AG\u5bf9\u95ed\u5408\u5934\u90e8\u635f\u4f24\uff08CHI\uff09\u5177\u6709\u795e\u7ecf\u4fdd\u62a4\u4f5c\u7528\uff0c\u5e76\u51cf\u8f7b\u4e86TBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\uff0c\u8868\u660e2-AG\u662f\u4e00\u79cd\u201c\u6309\u9700\u5236\u9020\u201d\u7684\u91cd\u8981\u5185\u6e90\u4fe1\u53f7\u4ecb\u8d28\uff0c\u7ef4\u62a4\u8111\u5185\u7a33\u6001\uff0c\u62b5\u5fa1\u6709\u5bb3\u4fb5\u5bb3\u3002\u7136\u800c\uff0c2-AG\u662f\u4e00\u79cd\u751f\u7269\u6d3b\u6027\u8102\u8d28\u4ecb\u8d28\uff0c\u4e00\u65e6\u751f\u6210\u5c31\u4f1a\u8fc5\u901f\u964d\u89e3\uff0c\u5305\u62ec\u5355\u9170\u7518\u6cb9\u8102\u9176\uff08MAGL\uff09\u3001a\/b\u6c34\u89e3\u9176\u7ed3\u6784\u57df\u542b\u6709\u7684\u86cb\u767d\u8d286\u548c12\uff08ABHD6\/12\uff09\u4ee5\u53ca\u73af\u6c27\u5408\u9176-2\uff08COX-2\uff09\u5728\u5185\u7684\u591a\u79cd\u9176\u90fd\u80fd\u964d\u89e32-AG\uff0c\u4f46\u4f30\u8ba1\u5927\u8111\u4e2d85%\u76842-AG\u662f\u901a\u8fc7MAGL\u6c34\u89e3\u7684\u30022-AG\u7684\u5373\u65f6\u4ee3\u8c22\u4ea7\u7269\u662f\u82b1\u751f\u56db\u70ef\u9178\uff0c\u662f\u524d\u5217\u817a\u7d20\u548c\u767d\u4e09\u70ef\u7684\u524d\u4f53\uff0c\u5206\u522b\u7531\u73af\u6c27\u5408\u9176-1\/2\u548c\u82b1\u751f\u56db\u70ef\u91785-\u8102\u6c27\u5408\u9176\uff08LOX\uff09\u50ac\u5316\u751f\u6210\u3002\u524d\u5217\u817a\u7d20\uff08\u5982PGE2\uff09\u548c\u767d\u4e09\u70ef\u4f3c\u4e4e\u662f\u795e\u7ecf\u9000\u884c\u6027\u75be\u75c5\u7684\u4fc3\u708e\u4ecb\u8d28\u3002\u8fd9\u8868\u660e\u901a\u8fc7\u6291\u5236MAGL\uff0c\u589e\u5f3a2-AG\u7684\u6297\u708e\u548c\u795e\u7ecf\u4fdd\u62a4\u4fe1\u53f7\uff0c\u540c\u65f6\u964d\u4f4e\u4fc3\u708e\u548c\u795e\u7ecf\u6bd2\u6027\u7684\u82b1\u751f\u56db\u70ef\u9178\u4ecb\u8d28\u6c34\u5e73\uff0c\u53ef\u80fd\u662f\u6cbb\u7597\u708e\u75c7\u6027\u548c\u795e\u7ecf\u9000\u884c\u6027\u75be\u75c5\u7684\u6709\u5e0c\u671b\u7684\u7b56\u7565<\/strong>\u3002\u4e8b\u5b9e\u4e0a\uff0c\u4ee5\u524d\u7684\u7814\u7a76\u8868\u660e\uff0cMAGL\u7684\u836f\u7269\u6291\u5236\u53ef\u4ee5\u7f13\u89e3\u795e\u7ecf\u708e\u75c7\u3001\u51cf\u8f7b\u795e\u7ecf\u75c5\u7406\uff0c\u6539\u5584\u591a\u79cd\u8111\u75be\u75c5\u7684\u52a8\u7269\u6a21\u578b\u4e2d\u7684\u7a81\u89e6\u548c\u8ba4\u77e5\u529f\u80fd\uff0c\u5305\u62ec\u963f\u5c14\u8328\u6d77\u9ed8\u75c5\u3001\u808c\u840e\u7f29\u6027\u4fa7\u7d22\u786c\u5316\u3001\u766b\u75eb\u3001\u591a\u53d1\u6027\u786c\u5316\u75c7\u548c\u5e15\u91d1\u68ee\u75c5\u3002\u6700\u8fd1\u7684\u51e0\u9879\u7814\u7a76\u7ed3\u679c\u8fdb\u4e00\u6b65\u8bc1\u660e\uff0c\u836f\u7269\u6291\u5236MAGL\u53ef\u4ee5\u51cf\u5c11\u8f7b\u5ea6TBI\u540e\u7684\u795e\u7ecf\u75c5\u7406\u53d8\u5316\uff0c\u6539\u5584\u7a81\u89e6\u53ef\u5851\u6027\u3001\u7a7a\u95f4\u5b66\u4e60\u548c\u8bb0\u5fc6\u3002\u7136\u800c\uff0c\u836f\u7269\u6291\u5236MAGL\u5728TBI\u4e2d\u5c55\u73b0\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\u7684\u673a\u5236\u5c1a\u4e0d\u6e05\u695a\u3002<\/p>\n

\u4e8c\u3001\u7814\u7a76\u65b9\u6cd5<\/h1>\n

\u7814\u7a76\u65b9\u6cd5\u4e3b\u8981\u5305\u62ec\u51c6\u5907KO\u52a8\u7269\u3001\u7ec6\u80de\u57f9\u517b\u3001 \u5efa\u7acb\u53cd\u590d\u8f7b\u5ea6\u95ed\u5408\u6027\u9885\u8111\u635f\u4f24\u6a21\u578b\u3001\u6d77\u9a6c\u7ec4\u7ec7\u5207\u7247\u3001\u7535\u751f\u7406\u8bb0\u5f55\u3001WB\u7b49\uff0c\u4e3b\u8981\u5173\u6ce8\u5355\u7ec6\u80de\u5206\u6790\u8fc7\u7a0b\u3002<\/p>\n

Single-cell RNA-seq data analysis
\nThe filtered unique molecular identifiers (UMI) feature-barcode matrices were produced byCellRanger Mkfatsq\/Count Analysis (10xGenomics.com), and Seurat R package (v3) was usedfor subsequent analysis 9. For quality control, cells with mitochondrial content > 30% and with <400 or > 6000 genes per cell were removed; and genes with a count of 1 in at least 20 cells wereretained. LogNormalize\u201d, a global-scaling normalization method, was used to normalize the databy a scale factor of 10000. Principal component analysis (PCA) was performed using the top 3000variable genes prior to clustering. To visualize profiles in two-dimensional space, t-distributedstochastic neighbor embedding (t-SNE) was performed with the top 20 principal componentsbased on the ElbowPlot. Clustering was performed using the FindClusters function (working onthe K-nearest neighbor graph model) in Seurat R package, and the resolution is 0.3. For identifyingthe cell type, \u2018aqp4\u2019, \u2018gja1\u2019, \u2018slc1a2\u2019 and \u2018gpr37l1\u2019 were used as specific cell markers forastrocytes, while \u2018aif1\u2019, \u2018itgam\u2019, \u2018csf1r\u2019, and \u2018tmem119\u2019 were used as specific cell markers formicroglia. These markers were used to assign cell-type annotations manually for each cell cluster.Differentially expressed genes (DEG) between Sham and TBI group were identified usingFindMarkers function of Seurat package in R, which works on the Wilcox method. Averaged log2(fold change) of gene expression, the percentage of cells expressing the genes in each group (pct.1and pct.2), p value and adjusted p value were generated. Min.pct = 0 and logfc. threshold = 0 wereused in finding DEGs. DEGs lists were produced by filtering all genes for log2 fold changes > 0.1and adjusted P < 0.05<\/p><\/blockquote>\n

    \n
  1. \u6570\u636e\u751f\u6210<\/strong>\uff1a\u901a\u8fc7CellRanger Mkfatsq\/Count Analysis\u8fdb\u884c\uff0c\u751f\u6210\u4e86\u7ecf\u8fc7\u7b5b\u9009\u7684UMI\u7279\u5f81\u6761\u5f62\u7801\u77e9\u9635\u3002<\/li>\n
  2. \u8d28\u91cf\u63a7\u5236<\/strong>\uff1a\u4ece\u6570\u636e\u4e2d\u79fb\u9664\u4e86\u7ebf\u7c92\u4f53\u542b\u91cf\u5927\u4e8e30%\u4ee5\u53ca\u6bcf\u4e2a\u7ec6\u80de\u7684\u57fa\u56e0\u6570\u5c0f\u4e8e400\u6216\u5927\u4e8e6000\u7684\u7ec6\u80de\uff0c\u4ee5\u786e\u4fdd\u5206\u6790\u7684\u8d28\u91cf\u3002\u540c\u65f6\uff0c\u4fdd\u7559\u4e86\u5728\u81f3\u5c1120\u4e2a\u7ec6\u80de\u4e2d\u81f3\u5c11\u67091\u6b21\u8ba1\u6570\u7684\u57fa\u56e0\u3002<\/li>\n
  3. \u6807\u51c6\u5316<\/strong>\uff1a\u4f7f\u7528\u201cLogNormalize\u201d\u65b9\u6cd5\u5bf9\u6570\u636e\u8fdb\u884c\u6807\u51c6\u5316\uff0c\u901a\u8fc7\u4e00\u4e2a\u89c4\u6a21\u56e0\u5b50\u5c06\u6570\u636e\u6807\u51c6\u5316\u523010000\u7684\u5c3a\u5ea6\u4e0a\u3002<\/li>\n
  4. \u4e3b\u6210\u5206\u5206\u6790\uff08PCA\uff09<\/strong>\uff1a\u5728\u8fdb\u884c\u805a\u7c7b\u4e4b\u524d\uff0c\u5bf9\u524d3000\u4e2a\u53ef\u53d8\u57fa\u56e0\u6267\u884cPCA\u3002<\/li>\n
  5. \u53ef\u89c6\u5316<\/strong>\uff1a\u4f7f\u7528t-distributed stochastic neighbor embedding\uff08t-SNE\uff09\u5c06\u6570\u636e\u5728\u4e8c\u7ef4\u7a7a\u95f4\u4e2d\u53ef\u89c6\u5316\uff0c\u57fa\u4e8eElbow Plot\u9009\u62e9\u524d20\u4e2a\u4e3b\u6210\u5206\u3002<\/li>\n
  6. \u805a\u7c7b<\/strong>\uff1a\u4f7f\u7528Seurat R\u5305\u4e2d\u7684FindClusters\u51fd\u6570\u8fdb\u884c\u805a\u7c7b\uff0c\u57fa\u4e8eK-nearest neighbor\u56fe\u6a21\u578b\uff0c\u5e76\u4e14\u8bbe\u7f6e\u5206\u8fa8\u7387\u4e3a0.3\u3002<\/li>\n
  7. \u7ec6\u80de\u7c7b\u578b\u9274\u5b9a<\/strong>\uff1a\u901a\u8fc7\u7279\u5b9a\u7ec6\u80de\u6807\u8bb0\u7269\uff08\u5982’aqp4’\u3001’gja1’\u3001’slc1a2’\u548c’gpr37l1’\u7528\u4e8e\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\uff0c’aif1’\u3001’itgam’\u3001’csf1r’\u548c’tmem119’\u7528\u4e8e\u5c0f\u80f6\u8d28\u7ec6\u80de\uff09\u6765\u624b\u52a8\u4e3a\u6bcf\u4e2a\u7ec6\u80de\u7c07\u5206\u914d\u7ec6\u80de\u7c7b\u578b\u6ce8\u91ca\u3002<\/li>\n
  8. \u5dee\u5f02\u8868\u8fbe\u57fa\u56e0\uff08DEG\uff09\u5206\u6790<\/strong>\uff1a\u4f7f\u7528Seurat\u5305\u4e2d\u7684FindMarkers\u51fd\u6570\u8fdb\u884c\uff0c\u4f7f\u7528Wilcox\u65b9\u6cd5\u8fdb\u884c\u5dee\u5f02\u8868\u8fbe\u57fa\u56e0\u5206\u6790\u3002\u751f\u6210\u4e86\u57fa\u56e0\u8868\u8fbe\u7684\u5e73\u5747log2(fold change)\u3001\u6bcf\u4e2a\u7ec4\u4e2d\u8868\u8fbe\u8be5\u57fa\u56e0\u7684\u7ec6\u80de\u767e\u5206\u6bd4\uff08pct.1\u548cpct.2\uff09\u3001p\u503c\u548c\u7ecf\u8fc7\u8c03\u6574\u7684p\u503c\u3002DEG\u5217\u8868\u901a\u8fc7\u7b5b\u9009\u51falog2\u6298\u53e0\u53d8\u5316> 0.1\u548c\u8c03\u6574\u540e\u7684P < 0.05\u7684\u6240\u6709\u57fa\u56e0\u6765\u751f\u6210\u3002<\/li>\n<\/ol>\n

    \u4e09\u3001\u7814\u7a76\u7ed3\u679c<\/h1>\n

    1.MAGL\u6761\u4ef6\u6572\u9664\u5c0f\u9f20\u7684\u4ea7\u751f\u4e0e\u7279\u6027\u5206\u6790<\/h2>\n

    \u524d\u671f\u7814\u7a76\u8868\u660e\uff0c\u4f7f\u7528JZL184\u7b49\u836f\u7269\u6765\u6291\u5236MAGL\u53ef\u4ee5\u7f13\u89e3TBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u3002\u4e3a\u4e86\u786e\u5b9a\u662f\u5426\u4e0e\u836f\u7269\u6291\u5236\u7c7b\u4f3c\uff0c\u9057\u4f20\u5220\u9664MAGL\u662f\u5426\u53ef\u4ee5\u51cf\u8f7bTBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\uff0c\u4ee5\u53caMAGL\u706d\u6d3b\u5f15\u8d77\u7684\u795e\u7ecf\u4fdd\u62a4\u4f5c\u7528\u662f\u5426\u4e0e\u7ec6\u80de\u7c7b\u578b\u6709\u5173\uff0c\u7814\u7a76\u8005\u4f7f\u7528\u4e86Mgll flox\/flox\u5c0f\u9f20\uff0c\u901a\u8fc7Supplementary Figs 1\u548c2A\u4e2d\u6240\u793a\u7684\u7b56\u7565\u751f\u6210\u4e86\u8fd9\u4e9b\u5c0f\u9f20\u3002\u7136\u540e\uff0c\u5229\u7528\u8fd9\u4e9b\u5c0f\u9f20\u751f\u6210\u4e86\u7279\u5b9a\u7ec6\u80de\u7c7b\u578b\u7684MAGL\u6572\u9664\u5c0f\u9f20\uff0c\u5305\u62ectKO\u3001nKO\u548caKO MAGL\u6572\u9664\u5c0f\u9f20\u7cfb\u5217\u3002<\/p>\n

    \u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u5728\u8fd9\u9879\u7814\u7a76\u4e2d\uff0c\u6ca1\u6709\u751f\u6210\u5c0f\u80f6\u8d28\u7ec6\u80deMAGL\u6572\u9664\u5c0f\u9f20\uff0c\u56e0\u4e3a\u5728\u5c0f\u80f6\u8d28\u7ec6\u80de\u4e2dMAGL\u5bf92-AG\u7684\u964d\u89e3\u4f5c\u7528\u4e0d\u663e\u8457\u3002\u65e9\u524d\u7814\u7a76\u5df2\u7ecf\u8bc1\u660e\uff0c\u5c0f\u80f6\u8d28\u7ec6\u80de\u4e2d\u4ea7\u751f\u76842-AG\u6570\u91cf\u5728\u5927\u8111\u4e2d\u7684\u603b2-AG\u5e93\u4e2d\u6240\u5360\u6bd4\u4f8b\u5fae\u4e0d\u8db3\u9053\uff0c\u800cMAGL\u5728\u5c0f\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684\u6572\u9664\u5e76\u4e0d\u4f1a\u6539\u53d8\u5927\u8111\u4e2d2-AG\u7684\u542b\u91cf\uff0c\u8fd9\u8868\u660eMAGL\u5728\u5c0f\u80f6\u8d28\u7ec6\u80de\u4e2d\u53ef\u80fd\u4e0d\u8d77\u964d\u89e32-AG\u7684\u91cd\u8981\u4f5c\u7528\u3002\u6700\u8fd1\u7684\u7814\u7a76\u4e5f\u8bc1\u5b9e\uff0c\u5c0f\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4e3b\u8981\u7531ABHD12\u6c34\u89e3\u3002<\/p>\n

    \u63a5\u4e0b\u6765\uff0c\u7814\u7a76\u8005\u901a\u8fc7\u4f53\u5916\u514d\u75ab\u5370\u8ff9\u9a8c\u8bc1\u4e86tKO\u3001nKO\u548caKO\u5c0f\u9f20\u4e2dMAGL\u7684\u9009\u62e9\u6027\u6572\u9664\u3002\u7ed3\u679c\u663e\u793a\uff0c\u4ecetKO\u548cnKO\u5c0f\u9f20\u57f9\u517b\u7684\u6d77\u9a6c\u795e\u7ecf\u5143\u4e2d\u672a\u68c0\u6d4b\u5230MAGL\u7684\u8868\u8fbe\uff0c\u4f46\u5728\u91ce\u751f\u578b\u548caKO\u5c0f\u9f20\u7684\u57f9\u517b\u6d77\u9a6c\u795e\u7ecf\u5143\u4e2d\u68c0\u6d4b\u5230\u4e86MAGL\u3002\u7c7b\u4f3c\u5730\uff0c\u4ecetKO\u548caKO\u5c0f\u9f20\u57f9\u517b\u7684\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u672a\u68c0\u6d4b\u5230MAGL\u7684\u8868\u8fbe\uff0c\u4f46\u4ece\u91ce\u751f\u578b\u548cnKO\u5c0f\u9f20\u7684\u57f9\u517b\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u68c0\u6d4b\u5230\u4e86MAGL\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0cMAGL\u88ab\u6761\u4ef6\u6027\u5220\u9664\u3002\u6b64\u5916\uff0c\u7ec6\u80de\u7c7b\u578b\u7279\u5f02\u6027\u7684MAGL\u6572\u9664\u5728\u4f53\u5185\u4e5f\u901a\u8fc7\u514d\u75ab\u5370\u8ff9\u3001\u5b9a\u91cf\u805a\u5408\u9176\u94fe\u53cd\u5e94\uff08qPCR\uff09\u548c\u514d\u75ab\u67d3\u8272\u7b49\u65b9\u6cd5\u5f97\u5230\u4e86\u8fdb\u4e00\u6b65\u7684\u786e\u8ba4\u3002<\/p>\n

    2. \u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684 MAGL \u5931\u6d3b\u53ef\u51cf\u5c11\u53cd\u590d\u8f7b\u5ea6\u95ed\u5934\u635f\u4f24\u540e\u7684\u795e\u7ecf\u708e\u75c7<\/h2>\n

    \u7814\u7a76\u9996\u5148\u901a\u8fc7\u68c0\u6d4b\u5927\u8111\u4e2d\u4e0e\u708e\u75c7\u76f8\u5173\u7684\u57fa\u56e0\uff08\u5305\u62ecVim\u548c\u7ec6\u80de\u56e0\u5b50Il1b\u3001Il6\u548cTnfa\uff09\u7684mRNA\u8868\u8fbe\u6765\u8bc4\u4f30\u795e\u7ecf\u708e\u75c7\u3002\u7ed3\u679c\u663e\u793a\uff0c\u5728\u63a5\u53d7\u4e86\u4e09\u6b21\u51b2\u51fb\u7684\u91ce\u751f\u578b\u5c0f\u9f20\u4e2d\uff0c\u8fd9\u4e9b\u57fa\u56e0\u7684\u8868\u8fbe\u663e\u8457\u589e\u52a0\uff0c\u800c\u5bf9\u7167\u7ec4\uff08\u91ce\u751f\u578b\u5c0f\u9f20\uff0c\u672a\u63a5\u53d7\u51b2\u51fb\uff09\u7684\u8868\u8fbe\u8f83\u4f4e\u3002\u4f46\u662f\uff0c\u5728\u5177\u6709\u9057\u4f20\u6572\u9664MAGL\u7684\u5c0f\u9f20\u4e2d\uff08tKO\u548caKO\uff09\uff0cTBI\u5f15\u53d1\u7684\u8fd9\u4e9b\u708e\u75c7\u56e0\u5b50\u7684\u8868\u8fbe\u663e\u8457\u964d\u4f4e\uff0c\u800c\u5728nKO\u5c0f\u9f20\u4e2d\u964d\u4f4e\u7a0b\u5ea6\u8f83\u5c0f\uff0c\u8fd9\u8868\u660e\u589e\u5f3a\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4fe1\u53f7\u5728\u89e3\u51b3TBI\u5f15\u53d1\u7684\u795e\u7ecf\u708e\u75c7\u4e2d\u8d77\u5230\u4e86\u81f3\u5173\u91cd\u8981\u7684\u4f5c\u7528\u3002<\/p>\n

    \u514d\u75ab\u67d3\u8272\u6570\u636e\u8fdb\u4e00\u6b65\u652f\u6301\u4e86\u4e0a\u8ff0\u53d1\u73b0\uff0c\u663e\u793a\u5728TBI\u540e\u768430\u5929\u5185\uff0c\u5177\u6709\u9057\u4f20\u6572\u9664MAGL\u7684\u5c0f\u9f20\uff08tKO\u548caKO\uff09\u4e2d\uff0cIb1a\uff08\u5c0f\u80f6\u8d28\u7ec6\u80de\u6807\u8bb0\u7269\uff09\u548cGFAP\uff08\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u6807\u8bb0\u7269\uff09\u7684\u514d\u75ab\u53cd\u5e94\u6027\u663e\u8457\u964d\u4f4e\u3002\u800c\u5728nKO\u5c0f\u9f20\u4e2d\uff0c\u8fd9\u79cd\u964d\u4f4e\u7a0b\u5ea6\u8f83\u5c0f\uff0c\u751a\u81f3\u53ef\u80fd\u6ca1\u6709\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0c\u901a\u8fc7\u836f\u7269\u6216\u5168\u5c40\u57fa\u56e0\u6572\u9664MAGL\uff0c\u80fd\u591f\u5728TBI\u4e2d\u4ea7\u751f\u6297\u708e\u75c7\u6548\u5e94\uff0c\u8fd9\u4e3b\u8981\u662f\u901a\u8fc7\u9650\u5236\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4ee3\u8c22\u800c\u975e\u795e\u7ecf\u5143\u4e2d\u76842-AG\u4ee3\u8c22\u6765\u5b9e\u73b0\u7684\u3002\u5f3a\u8c03\u4e86\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d2-AG\u4fe1\u53f7\u7684\u91cd\u8981\u6027\uff0c\u4ee5\u89e3\u51b3TBI\u5f15\u53d1\u7684\u795e\u7ecf\u708e\u75c7\u3002<\/p>\n

    3.\u6291\u5236\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684 2-AG \u4ee3\u8c22\u53ef\u589e\u5f3a\u5bf9\u521b\u4f24\u6027\u8111\u635f\u4f24\u5f15\u8d77\u7684\u53d8\u5316\u7684\u6062\u590d\u80fd\u529b\uff0c\u51cf\u5c11\u708e\u75c7\u76f8\u5173\u57fa\u56e0\u7684\u8868\u8fbe<\/h2>\n

    \u7531\u4e8e\u795e\u7ecf\u708e\u75c7\u5728\u673a\u68b0\u6027\u521b\u4f24\u540e\u5f15\u53d1\u6b21\u751f\u8111\u635f\u4f24\u4e2d\u8d77\u7740\u5173\u952e\u4f5c\u7528\uff0c\u800c\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u548c\u5c0f\u80f6\u8d28\u7ec6\u80de\u662f\u795e\u7ecf\u708e\u75c7\u7684\u4e3b\u8981\u53c2\u4e0e\u8005\uff0c\u56e0\u6b64\u7814\u7a76\u8005\u4f7f\u7528\u4e8610x Genomics Chromium scRNA-seq\u6280\u672f\u6765\u8bc4\u4f30\u91ce\u751f\u578b\u3001nKO\u548caKO\u5c0f\u9f20\u4e2d\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u548c\u5c0f\u80f6\u8d28\u7ec6\u80de\u7684\u57fa\u56e0\u8868\u8fbe\u60c5\u51b5\uff0c\u8fd9\u4e9b\u5c0f\u9f20\u63a5\u53d7\u4e86\u4e09\u6b21mCHI\u3002<\/p>\n

    \u5728\u8fd9\u9879\u7814\u7a76\u4e2d\uff0cAqp4\u3001Gja1\u3001Slc1a2\u548cGpr37l1\u88ab\u7528\u4f5c\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u7684\u7279\u5b9a\u7ec6\u80de\u6807\u8bb0\u7269\uff0c\u800cAif1\u3001Itgam\u3001Csf1r\u548cTmem119\u88ab\u7528\u4f5c\u5c0f\u80f6\u8d28\u7ec6\u80de\u7684\u7279\u5b9a\u7ec6\u80de\u6807\u8bb0\u7269\u3002\u901a\u8fc710x Genomics Chromium scRNA-seq\u6280\u672f\uff0c\u7814\u7a76\u8005\u8bc4\u4f30\u4e86\u8fd9\u4e9b\u7ec6\u80de\u7c7b\u578b\u7684\u57fa\u56e0\u8868\u8fbe\u3002<\/p>\n

    \u7814\u7a76\u7ed3\u679c\u663e\u793a\uff0cTBI\u5bfc\u81f4\u4e86\u91ce\u751f\u578b\u548cnKO\u5c0f\u9f20\u7684\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u548c\u5c0f\u80f6\u8d28\u7ec6\u80de\u4e2d\u5927\u91cf\u57fa\u56e0\u7684\u4e0a\u8c03\u6216\u4e0b\u8c03\u8868\u8fbe\uff0c\u4f46\u5728aKO\u5c0f\u9f20\u4e2d\u7684\u6548\u5e94\u8f83\u5c0f\u3002\u5c24\u5176\u91cd\u8981\u7684\u662f\uff0c\u5728\u91ce\u751f\u578b\u548cnKO\u5c0f\u9f20\u4e2d\uff0cTBI\u5bfc\u81f4\u4e86\u4e0e\u708e\u75c7\u6709\u5173\u7684\u57fa\u56e0\u4e0a\u8c03\uff0c\u4e0e\u6297\u708e\u75c7\u53cd\u5e94\u6216\u5927\u8111\u7a33\u6001\u7ef4\u6301\u76f8\u5173\u7684\u57fa\u56e0\u4e0b\u8c03\uff08Ccl12, Ccl4, Ccl7, Ptgs2, Ccl3, Cx3cr1, P2ry12, and Cd86 \uff09\u3002\u800c\u5728aKO\u5c0f\u9f20\u4e2d\uff0c\u8fd9\u4e9b\u6548\u5e94\u8f83\u5c0f\u3002<\/p>\n

    \"\u56fe\u7247[1]-\u5403\u4e86\u5403\u4e86\"<\/p>\n

    \u6b64\u5916\uff0c\u57fa\u56e0\u8868\u8fbe\u5dee\u5f02\u5206\u6790\u8fd8\u663e\u793a\uff0c\u5728\u91ce\u751f\u578b\u548cnKO\u5c0f\u9f20\u7684\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u548c\u5c0f\u80f6\u8d28\u7ec6\u80de\u4e2d\uff0c\u66f4\u591a\u53c2\u4e0e\u514d\u75ab\u548c\u708e\u75c7\u4fe1\u53f7\u901a\u8def\u7684\u57fa\u56e0\u4e0a\u8c03\uff0c\u800c\u5728aKO\u5c0f\u9f20\u4e2d\u4e0a\u8c03\u7684\u57fa\u56e0\u8f83\u5c11\u3002<\/p>\n

    \u5355\u7ec6\u80de\u6d4b\u5e8f\u6570\u636e\u8868\u660e\uff0c\u901a\u8fc7\u6291\u5236\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4ee3\u8c22\uff0c\u53ef\u4ee5\u4f7f\u5927\u8111\u66f4\u5177\u62b5\u6297TBI\u5f15\u53d1\u7684\u795e\u7ecf\u708e\u75c7\u76f8\u5173\u57fa\u56e0\u8868\u8fbe\u53d8\u5316\u7684\u80fd\u529b\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0c\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d2-AG\u4fe1\u53f7\u7684\u8c03\u8282\u5728\u51cf\u8f7bTBI\u5f15\u53d1\u7684\u795e\u7ecf\u708e\u75c7\u65b9\u9762\u53d1\u6325\u4e86\u5173\u952e\u4f5c\u7528\u3002<\/p>\n

    4.\u9009\u62e9\u6027\u5931\u6d3b\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684 MAGL \u53ef\u964d\u4f4eTBI\u8bf1\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u53d8\u5316<\/h2>\n

    TDP-43\u548c\u8fc7\u5ea6\u78f7\u9178\u5316tau\uff08p-tau\uff09\u7684\u805a\u96c6\u662fTBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u7684\u6807\u5fd7\u3002\u4ee5\u524d\u7684\u7814\u7a76\u5df2\u7ecf\u8868\u660e\uff0c\u901a\u8fc7\u836f\u7269\u6291\u5236MAGL\u53ef\u4ee5\u663e\u8457\u964d\u4f4eTBI\u52a8\u7269\u4e2dTDP-43\u548cp-tau\u7684\u8868\u8fbe\u3002\u4e3a\u4e86\u786e\u5b9a\u9057\u4f20\u6572\u9664MAGL\u662f\u5426\u4e5f\u80fd\u9632\u6b62TBI\u5f15\u53d1\u7684TDP-43\u8fc7\u5ea6\u751f\u6210\u548cp-tau\uff0c\u7814\u7a76\u8005\u5728\u63a5\u53d7\u4e86\u4e09\u6b21mCHI\u51b2\u51fb\u7684\u91ce\u751f\u578b\u3001tKO\u3001nKO\u548caKO\u5c0f\u9f20\u4e2d\uff0c\u5728\u7b2c\u4e00\u6b21\u51b2\u51fb\u540e\u768430\u5929\u5185\u8bc4\u4f30\u4e86TDP-43\u548cp-tau-T181\uff08p-tau\uff09\u6c34\u5e73\u3002\u4ed6\u4eec\u53d1\u73b0\uff0c\u91cd\u590d\u7684mCHI\u663e\u8457\u63d0\u9ad8\u4e86\u91ce\u751f\u578b\u5c0f\u9f20\u7684TDP-43\u548cp-tau\u6c34\u5e73\uff0c\u4f46\u6ca1\u6709\u5728tKO\u548caKO\u5c0f\u9f20\u4e2d\u89c2\u5bdf\u5230\u8fd9\u79cd\u589e\u52a0\u3002\u4ee4\u4eba\u60ca\u8bb6\u7684\u662f\uff0cTBI\u540enKO\u5c0f\u9f20\u7684TDP-43\u548cp-tau\u6c34\u5e73\u663e\u8457\u5347\u9ad8\uff0c\u4e0e\u91ce\u751f\u578b\u5c0f\u9f20\u7c7b\u4f3c\u3002\u7814\u7a76\u8fd8\u8bc4\u4f30\u4e86tau\u5728\u989d\u89d2\u53f6\u7684\u5176\u4ed6\u78f7\u9178\u5316\u4f4d\u70b9\uff08p-tau-Ser202\u3001p-tau-Thr231\u3001p-tau-Ser396\u548cp-tau-Ser404\uff09\u7684\u6c34\u5e73\uff0c\u53d1\u73b0TBI\u5bfc\u81f4\u4e86\u91ce\u751f\u578b\u548cnKO\u5c0f\u9f20\u4e2dp-tau Ser202\u3001Thr231\u3001Ser396\u548cSer404\u7684\u663e\u8457\u589e\u52a0\uff0c\u4f46\u5728tKO\u548caKO\u5c0f\u9f20\u4e2d\u672a\u89c2\u5bdf\u5230\u8fd9\u79cd\u589e\u52a0\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0c\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u964d\u89e3\u5728TBI\u5f15\u53d1\u7684TDP-43\u8fc7\u5ea6\u751f\u6210\u548c\u591a\u4e2a\u4f4d\u70b9\u7684tau\u78f7\u9178\u5316\u4e2d\u8d77\u91cd\u8981\u4f5c\u7528\uff0c\u901a\u8fc7\u6291\u5236MAGL\u7684\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4ee3\u8c22\uff0c\u53ef\u4ee5\u9884\u9632TBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u53d8\u5316\u3002<\/p>\n

    \u8111\u5f25\u6f2b\u6027\u8f74\u7d22\u635f\u4f24\u5df2\u88ab\u8ba4\u4e3a\u662fTBI\u6700\u5e38\u89c1\u548c\u91cd\u8981\u7684\u75c5\u7406\u7279\u5f81\u4e4b\u4e00\u3002APP\u7684\u8868\u8fbe\u5728TBI\u540e\u4f1a\u589e\u52a0\uff0c\u800cAPP\u4e0d\u4ec5\u662f\u6dc0\u7c89\u6837\u86cb\u767d\u03b2\u7684\u524d\u4f53\uff0c\u8fd8\u662fTBI\u540e\u5f25\u6f2b\u6027\u8f74\u7d22\u635f\u4f24\u7684\u91cd\u8981\u6807\u5fd7\u3002\u7814\u7a76\u8005\u8bc4\u4f30\u4e86TBI\u5f15\u53d1\u7684\u8f74\u7d22\u635f\u4f24\u662f\u5426\u5f97\u5230\u4e86\u9057\u4f20\u6572\u9664MAGL\u7684\u7f13\u89e3\u3002\u7ed3\u679c\u663e\u793a\uff0c\u5728\u63a5\u53d7\u4e86\u4e09\u6b21\u51b2\u51fb\u7684\u91ce\u751f\u578b\u548cnKO\u5c0f\u9f20\u4e2d\uff0c\u5927\u8111\u76ae\u8d28\u548c\u6d77\u9a6c\u4e2d\u7684APP\u663e\u8457\u5347\u9ad8\uff0c\u4f46\u5728tKO\u548caKO\u5c0f\u9f20\u4e2d\u6ca1\u6709\u89c2\u5bdf\u5230\u8fd9\u79cd\u589e\u52a0\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0c\u9650\u5236\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u964d\u89e3\u53ef\u4ee5\u9884\u9632TBI\u5f15\u53d1\u7684\u8f74\u7d22\u635f\u4f24\u3002<\/p>\n

    \u795e\u7ecf\u9000\u884c\u6027\u75c5\u53d8\u662fTBI\u7684\u91cd\u8981\u795e\u7ecf\u75c5\u7406\u7279\u5f81\u4e4b\u4e00\u3002\u4ee5\u524d\u7684\u7814\u7a76\u5df2\u7ecf\u8868\u660e\uff0cTBI\u540e\u63a5\u53d7JZL184\uff08\u4e00\u79cd\u5f3a\u6548MAGL\u6291\u5236\u5242\uff09\u6cbb\u7597\u7684\u52a8\u7269\u4e2d\uff0c\u9000\u884c\u6027\u795e\u7ecf\u5143\u7684\u6570\u91cf\u663e\u8457\u51cf\u5c11\u3002\u4e3a\u4e86\u786e\u5b9aMAGL\u7684\u6572\u9664\u662f\u5426\u4e5f\u80fd\u51cf\u5c11TBI\u540e\u7684\u795e\u7ecf\u9000\u884c\u6027\u75c5\u53d8\uff0c\u7814\u7a76\u8005\u8bc4\u4f30\u4e86\u53d7\u5230\u91cd\u590dmCHI\u5f71\u54cd\u7684\u5c0f\u9f20\u5927\u8111\u4e2dFluoro-JadeVR C\uff08\u795e\u7ecf\u9000\u884c\u6027\u6807\u5fd7\u7269\uff09\u9633\u6027\u795e\u7ecf\u5143\u7684\u6570\u91cf<\/strong>\u3002\u4ed6\u4eec\u53d1\u73b0\uff0c\u91cd\u590d\u7684mCHI\u663e\u8457\u589e\u52a0\u4e86\u91ce\u751f\u578b\u5c0f\u9f20\u5728\u51b2\u51fb\u540e30\u5929\u5185\u76ae\u8d28\u548c\u6d77\u9a6c\u4e2dFluoro-JadeVR C\u9633\u6027\u795e\u7ecf\u5143\u7684\u6570\u91cf\uff08\u56fe4B\uff09\u3002\u9884\u671f\u5730\uff0cMAGL\u6572\u9664\u5c0f\u9f20\u4e2d\u7684\u9000\u884c\u6027\u795e\u7ecf\u5143\u6570\u91cf\u4e5f\u663e\u8457\u51cf\u5c11\u3002\u7136\u800c\uff0c\u4e0etKO\u6216aKO\u5c0f\u9f20\u76f8\u6bd4\uff0cnKO\u5c0f\u9f20\u4e2d\u7684\u9000\u884c\u6027\u795e\u7ecf\u5143\u51cf\u5c11\u5e45\u5ea6\u8981\u5c0f\u5f97\u591a\u3002\u8fd9\u4e9b\u6570\u636e\u8868\u660e\uff0c\u901a\u8fc7\u836f\u7269\u6291\u5236\u6216\u5168\u5c40\u6572\u9664MAGL\uff0c\u5728TBI\u540e\u51cf\u5c11\u7684\u795e\u7ecf\u9000\u884c\u6027\u4e3b\u8981\u662f\u901a\u8fc7\u6291\u5236\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4ee3\u8c22\u800c\u4ea7\u751f\u7684\u3002<\/p>\n

    \u603b\u4e4b\uff0c\u7814\u7a76\u53d1\u73b0\u901a\u8fc7\u9650\u5236\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u964d\u89e3\uff0c\u53ef\u4ee5\u5728\u591a\u4e2a\u65b9\u9762\u51cf\u8f7bTBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u53d8\u5316\uff0c\u5305\u62ec\u51cf\u5c11TDP-43\u8fc7\u5ea6\u751f\u6210\u3001\u51cf\u8f7btau\u5728\u591a\u4e2a\u4f4d\u70b9\u7684\u78f7\u9178\u5316\u3001\u9884\u9632\u8f74\u7d22\u635f\u4f24\u548c\u964d\u4f4e\u795e\u7ecf\u9000\u884c\u6027\u75c5\u53d8\u3002\u8fd9\u4e9b\u7ed3\u679c\u7a81\u663e\u4e862-AG\u4fe1\u53f7\u901a\u8def\u5728TBI\u6cbb\u7597\u4e2d\u7684\u91cd\u8981\u6027\uff0c\u5c24\u5176\u662f\u5176\u5728\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684\u4f5c\u7528\u3002<\/p>\n

    \u9700\u8981\u6ce8\u610f\u7684\u662f\uff0c\u5728\u8fd9\u4e9b\u7814\u7a76\u7ed3\u679c\u4e2d\uff0ctKO\u548caKO\u5c0f\u9f20\uff08\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2dMAGL\u88ab\u6572\u9664\u7684\u5c0f\u9f20\uff09\u5728\u591a\u4e2a\u65b9\u9762\u8868\u73b0\u51fa\u660e\u663e\u7684\u795e\u7ecf\u4fdd\u62a4\u4f5c\u7528\uff0c\u800cnKO\u5c0f\u9f20\uff08\u795e\u7ecf\u5143\u4e2dMAGL\u88ab\u6572\u9664\u7684\u5c0f\u9f20\uff09\u7684\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\u8f83\u5c0f\u3002\u8fd9\u8868\u660e\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4fe1\u53f7\u901a\u8def\u5728TBI\u540e\u7684\u795e\u7ecf\u4fdd\u62a4\u4e2d\u8d77\u5230\u5173\u952e\u4f5c\u7528\u3002<\/p>\n

    5.\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684 MAGL \u5931\u6d3b\u53ef\u9884\u9632\u521b\u4f24\u6027\u8111\u635f\u4f24\u5f15\u8d77\u7684\u7a81\u89e6\u548c\u8ba4\u77e5\u529f\u80fd\u9000\u5316<\/h2>\n

    \u4e3a\u4e86\u786e\u5b9a\u901a\u8fc7\u9057\u4f20\u6572\u9664MAGL\u6765\u6291\u52362-AG\u964d\u89e3\u662f\u5426\u53ef\u4ee5\u9884\u9632TBI\u5f15\u53d1\u7684\u957f\u671f\u7a81\u89e6\u53ef\u5851\u6027\u3001\u5b66\u4e60\u548c\u8bb0\u5fc6\u53d7\u635f\uff0c\u7814\u7a76\u8005\u4f7f\u7528\u7535\u751f\u7406\u8bb0\u5f55\u8bc4\u4f30\u4e86\u6d77\u9a6cSchaffer\u652f\u6491\u7ea4\u7ef4\u7a81\u89e6\u7684\u957f\u65f6\u7a0b\u589e\u5f3a<\/strong>\u3002\u8fd9\u4e9b\u6d4b\u8bd5\u662f\u5728\u7b2c\u4e00\u6b21TBI\u51b2\u51fb\u540e\u768430\u5929\u5185\u8fdb\u884c\u7684\u3002\u4ed6\u4eec\u53d1\u73b0\uff0c\u91cd\u590d\u7684mCHI\u663e\u8457\u635f\u5bb3\u4e86\u91ce\u751f\u578b\u5c0f\u9f20\u7684\u6d77\u9a6c\u957f\u65f6\u7a0b\u589e\u5f3a\uff08\u56fe5A\u548cB\uff09\u3002\u7136\u800c\uff0cTBI\u5f15\u53d1\u7684\u957f\u65f6\u7a0b\u7a81\u89e6\u53ef\u5851\u6027\u635f\u5bb3\u5728tKO\u548caKO\u5c0f\u9f20\u4e2d\u5f97\u4ee5\u907f\u514d\uff0c\u4f46\u5728nKO\u5c0f\u9f20\u4e2d\u672a\u89c2\u5bdf\u5230\u8fd9\u79cd\u60c5\u51b5\u3002\u7814\u7a76\u8005\u8fd8\u4f7f\u7528Morris\u6c34\u8ff7\u5bab\u6d4b\u8bd5\u8bc4\u4f30\u4e86\u7a7a\u95f4\u5b66\u4e60\u548c\u8bb0\u5fc6<\/strong>\u3002\u4e0e\u91ce\u751f\u578b\u5c0f\u9f20\u76f8\u6bd4\uff0cTBI\u5f15\u53d1\u7684\u7a7a\u95f4\u5b66\u4e60\u548c\u8bb0\u5fc6\u7f3a\u9677\u5728tKO\u548caKO\u5c0f\u9f20\u4e2d\u5f97\u4ee5\u9884\u9632\uff0c\u4f46\u5728nKO\u5c0f\u9f20\u4e2d\u672a\u89c2\u5bdf\u5230\u8fd9\u79cd\u60c5\u51b5\uff08\u56fe5C\u548cD\u4ee5\u53ca\u8865\u5145\u56fe8\uff09\u3002\u51fa\u4e4e\u610f\u6599\u7684\u662f\uff0csham-nKO\u5c0f\u9f20\u663e\u793a\u51fa\u7a7a\u95f4\u5b66\u4e60\u548c\u8bb0\u5fc6\u53d7\u635f\uff08\u56fe5C\u548cD\uff09\uff0c\u8fd9\u8868\u660e\u795e\u7ecf\u5143\u4e2d\u76842-AG\u6b63\u5e38\u964d\u89e3\u5bf9\u4e8e\u6b63\u5e38\u7684\u8ba4\u77e5\u529f\u80fd\u662f\u5fc5\u8981\u7684\u3002\u7814\u7a76\u8005\u8fd8\u6ce8\u610f\u5230\uff0c\u5728aKO\u5c0f\u9f20\u4e2d\uff0cTBI\u5f15\u53d1\u7684\u5b66\u4e60\u548c\u8bb0\u5fc6\u53d7\u635f\u5b8c\u5168\u6d88\u5931\uff0c\u4f46\u5728tKO\u5c0f\u9f20\u4e2d\u672a\u89c2\u5bdf\u5230\u8fd9\u79cd\u60c5\u51b5\uff08\u56fe5C\u548cD\uff09\u3002\u8fd9\u53ef\u80fd\u662f\u56e0\u4e3atKO\u5c0f\u9f20\u4e2d\u795e\u7ecf\u5143MAGL\u7684\u5931\u6d3b\u4f1a\u52a0\u91cdMorris\u6c34\u8ff7\u5bab\u6d4b\u8bd5\u7684\u8868\u73b0\u3002\u7814\u7a76\u6570\u636e\u63d0\u4f9b\u4e86\u8bc1\u636e\uff0c\u901a\u8fc7\u5728\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u5931\u6d3bMAGL\u6765\u9650\u52362-AG\u4ee3\u8c22\u53ef\u4ee5\u5728\u8111\u635f\u4f24\u540e\u7ef4\u6301\u5927\u8111\u529f\u80fd\u7684\u7a33\u6001\u3002<\/p>\n

    \"\u56fe\u7247[2]-\u5403\u4e86\u5403\u4e86\"<\/p>\n

    6.\u4e2d\u65ad\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684 2-AG \u4ee3\u8c22\u53ef\u9632\u6b62 TBI \u5bfc\u81f4\u7684\u8c37\u6c28\u9178\u53d7\u4f53\u4e9a\u57fa\u8868\u8fbe\u51cf\u5c11<\/h2>\n

    \u91cd\u590d\u6027mCHI\u4f1a\u5bfc\u81f4\u8c37\u6c28\u9178\u53d7\u4f53\u4e9a\u5355\u4f4d\u8868\u8fbe\u4e0b\u8c03\uff0c\u8fd9\u4e9b\u4e9a\u5355\u4f4d\u662f\u5174\u594b\u6027\u7a81\u89e6\u4f20\u9012\u548c\u53ef\u5851\u6027\u7684\u5173\u952e\u7ec4\u6210\u90e8\u5206\uff0c\u800cMAGL\u7684\u836f\u7269\u6291\u5236\u53ef\u4ee5\u9632\u6b62TBI\u5f15\u53d1\u7684\u8fd9\u4e9b\u4e9a\u5355\u4f4d\u7684\u4e0b\u8c03\u3002\u7814\u7a76\u4eba\u5458\u9884\u6d4b\uff0cMAGL\u7684\u6572\u9664\u5e94\u8be5\u53ef\u4ee5\u9632\u6b62TBI\u5f15\u53d1\u7684\u8c37\u6c28\u9178\u53d7\u4f53\u4e9a\u5355\u4f4d\u8868\u8fbe\u7684\u6076\u5316\u3002TBI\u5bfc\u81f4\u91ce\u751f\u578b\u5c0f\u9f20\u5728\u51b2\u51fb\u540e30\u5929\u7684\u6d77\u9a6c\u4e2d\uff0cAMPA\u53d7\u4f53\u4e9a\u5355\u4f4d\uff08\u5305\u62ecGluA1\u548cGluA2\uff09\u548cNMDA\u53d7\u4f53\u4e9a\u5355\u4f4d\uff08\u5305\u62ecGluN1\u3001GluN2A\u548cGluN2B\uff09\u7684\u660e\u663e\u4e0b\u8c03\uff08\u56fe5E-G\uff09\u3002\u7136\u800c\uff0c\u5728tKO\u548caKO\u5c0f\u9f20\u4e2d\uff0cTBI\u5f15\u53d1\u7684\u8fd9\u4e9b\u4e9a\u5355\u4f4d\u7684\u4e0b\u8c03\u660e\u663e\u51cf\u8f7b\uff0c\u4f46\u5728nKO\u5c0f\u9f20\u4e2d\u672a\u89c2\u5bdf\u5230\u8fd9\u79cd\u60c5\u51b5\uff08\u56fe5E-G\uff09\u3002\u7814\u7a76\u4eba\u5458\u8fd8\u89c2\u5bdf\u5230\uff0c\u4e0e\u91ce\u751f\u578b\u5c0f\u9f20\u76f8\u6bd4\uff0csham nKO\u5c0f\u9f20\u4e2dGluA1\u548cGluA2\u7684\u8868\u8fbe\u663e\u8457\u964d\u4f4e\uff08\u56fe5F\uff09\u3002\u8fd9\u53ef\u80fd\u662f\u5bfc\u81f4nKO\u5c0f\u9f20\u7684\u7a7a\u95f4\u5b66\u4e60\u548c\u8bb0\u5fc6\u53d7\u635f\uff0c\u5982\u56fe5C\u548cD\u6240\u793a\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0c\u901a\u8fc7\u6291\u5236\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4ee3\u8c22\uff0c\u53ef\u4ee5\u901a\u8fc7\u7ef4\u6301\u5174\u594b\u6027\u8c37\u6c28\u9178\u7a81\u89e6\u7684\u5b8c\u6574\u6027<\/strong>\u6765\u9632\u6b62TBI\u5f15\u53d1\u7684\u7a81\u89e6\u548c\u8ba4\u77e5\u4e0b\u964d\u3002<\/p>\n

    7.\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d MAGL \u7684\u8868\u8fbe\u5347\u9ad8<\/h2>\n

    \u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4ee3\u8c22\u4fc3\u8fdb\u4e86TBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u548c\u7a81\u89e6\u4ee5\u53ca\u8ba4\u77e5\u4e0b\u964d\u3002\u7814\u7a76\u4eba\u5458\u5047\u8bbeTBI\u53ef\u80fd\u901a\u8fc7\u63d0\u9ad8\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2dMAGL\u7684\u8868\u8fbe\u6765\u52a0\u901f2-AG\u7684\u964d\u89e3\uff0c\u4ece\u800c\u4fc3\u8fdb\u795e\u7ecf\u708e\u75c7\u53cd\u5e94\u548c\u795e\u7ecf\u75c5\u7406\u6027\u53d8\u5316\u3002\u4e3a\u4e86\u9a8c\u8bc1\u8fd9\u4e00\u5047\u8bbe\uff0c\u7814\u7a76\u4eba\u5458\u8bc4\u4f30\u4e86TBI\u540e\u91ce\u751f\u578b\u5c0f\u9f20\u4e2dMAGL\u7684\u8868\u8fbe\u3002\u7814\u7a76\u4eba\u5458\u53d1\u73b0\uff0c\u5728TBI\u540e\uff0c\u5927\u8111\u4e2d\u7684MAGL\u8868\u8fbe\u4e0a\u5347\uff08\u9644\u56fe9A\uff09\u3002\u7531\u4e8e\u7528\u4e8e\u514d\u75ab\u5370\u8ff9\u5206\u6790\u7684\u5747\u8d28\u5316\u8111\u7ec4\u7ec7\u6837\u672c\u5305\u542b\u4e86\u6240\u6709\u7c7b\u578b\u7684\u7ec6\u80de\uff0c\u56e0\u6b64\u7814\u7a76\u4eba\u5458\u60f3\u77e5\u9053MAGL\u7684\u8868\u8fbe\u589e\u52a0\u662f\u5426\u4e3b\u8981\u662f\u7531\u4e8eTBI\u540e\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u6570\u91cf\u589e\u52a0\u3002\u4e3a\u6b64\uff0c\u7814\u7a76\u4eba\u5458\u4f7f\u7528\u53cc\u91cd\u514d\u75ab\u67d3\u8272\u6765\u68c0\u6d4bGFAP\u9633\u6027\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2dMAGL\u7684\u8868\u8fbe\uff0c\u5e76\u89c2\u5bdf\u5230GFAP\u9633\u6027\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684MAGL\u8868\u8fbe\u663e\u8457\u4e0a\u5347\uff08\u9644\u56fe9B\uff09\u3002\u9274\u4e8e\u8fd9\u4e9b\u53d1\u73b0\uff0c\u7814\u7a76\u4eba\u5458\u5728\u7ec6\u80de\u7c7b\u578b\u7279\u5f02\u6027MAGL\u6572\u9664\u5c0f\u9f20\u4e2d\u901a\u8fc7\u8d28\u8c31\u5206\u6790\u8bc4\u4f30\u4e86\u5927\u8111\u4e2d\u76842-AG\u3002\u7814\u7a76\u4eba\u5458\u53d1\u73b0\uff0c\u5728\u5bf9\u7167\u6761\u4ef6\u4e0b\uff0ctKO\u5c0f\u9f20\u76842-AG\u542b\u91cf\u589e\u52a0\u4e867\u500d\u4ee5\u4e0a\uff0cnKO\u5c0f\u9f20\u589e\u52a0\u4e865\u500d\uff0c\u800caKO\u5c0f\u9f20\u589e\u52a0\u4e86\u7ea62\u500d\uff0c\u8fd9\u8868\u660e\u5927\u8111\u4e2d\u7684\u5927\u90e8\u52062-AG\u662f\u7531\u795e\u7ecf\u5143\u4e2d\u7684MAGL\u4ee3\u8c22\u7684\uff08\u9644\u56fe9C\uff09\u3002\u8fd9\u4e9b\u6570\u636e\u4e0e\u5148\u524d\u7684\u62a5\u544a\u4e00\u81f4\u3002\u7136\u800c\uff0c\u5728\u6bcf\u79cd\u57fa\u56e0\u578b\u4e2d\uff0cTBI\u540e24\u5c0f\u65f6\u68c0\u6d4b\u5230\u7684\u5927\u81112-AG\u6c34\u5e73\u4e0esham\u7ec4\u76f8\u6bd4\u6ca1\u6709\u663e\u8457\u53d8\u5316\uff08\u9644\u56fe9C\uff09\u3002\u8fd9\u53ef\u80fd\u662f\u7531\u4e8e\u5728\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u4ea7\u751f\u76842-AG\u76f8\u5bf9\u8f83\u5c11\uff0c\u5bf9\u5927\u8111\u4e2d\u7684\u603b2-AG\u6c60\u7684\u8d21\u732e\u8f83\u5c0f\u3002<\/p>\n

    8.MAGL \u5931\u6d3b\u7f13\u89e3\u795e\u7ecf\u75c5\u7406\u5b66\u548c\u8ba4\u77e5\u80fd\u529b\u4e0b\u964d\u662f\u901a\u8fc7 CB1R \u4ecb\u5bfc\u7684<\/h2>\n

    \u901a\u8fc7\u5728\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u9057\u4f20\u6027\u5220\u9664MAGL\u53ef\u4ee5\u51cf\u8f7bTBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u5b66\u95ee\u9898\uff0c\u5e76\u9884\u9632\u7a81\u89e6\u548c\u8ba4\u77e5\u529f\u80fd\u7684\u4e0b\u964d\uff0c\u8fd9\u4e0e\u4e4b\u524d\u7684\u7814\u7a76\u7ed3\u679c\u4f7f\u7528JZL184\u76f8\u4f3c\u3002\u7136\u800c\uff0c\u76ee\u524d\u5c1a\u4e0d\u6e05\u695a\u901a\u8fc7\u661f\u5f62\u80f6\u8d28\u7ec6\u80deMAGL\u7684\u5931\u6d3b\u5728TBI\u4e2d\u4ea7\u751f\u7684\u6709\u76ca\u6548\u679c\u662f\u5426\u662f\u901a\u8fc7\u589e\u5f3a2-AG\u4fe1\u53f7\u4f20\u5bfc\u53ca\u5176\u4e0b\u6e38\u4ecb\u8d28CB1R\u6216CB2R\u4ecb\u5bfc\u7684\u3002\u4e3a\u4e86\u786e\u5b9aCB1R\u662f\u5426\u4ecb\u5bfcMAGL\u5931\u6d3b\u4ea7\u751f\u7684\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\uff0cCB1R\u6572\u9664\u5c0f\u9f20\u5728\u6bcf\u6b21\u51b2\u51fb\u540e30\u5206\u949f\u548c\u8fde\u7eed\u56db\u5929\u5185\u6bcf\u5929\u4e00\u6b21\uff08\u603b\u5171\u4e03\u6b21\u6ce8\u5c04\uff09\u8179\u8154\u6ce8\u5c04JZL184\uff0810mg\/kg\uff09\u6216\u8f7d\u4f53\uff0c\u5982\u5148\u524d\u6240\u8ff0\uff08\u9644\u56fe2C\uff09\u3002\u867d\u7136JZL184\u9884\u9632\u4e86\u91ce\u751f\u578b\u5c0f\u9f20\u4e2dTBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u5b66\u95ee\u9898\u548c\u8ba4\u77e5\u529f\u80fd\u969c\u788d\uff08\u56fe6A\u548cB\uff09\uff0c\u4e0e\u4e4b\u524d\u7684\u89c2\u5bdf\u76f8\u4f3c\uff0c\u4f46\u6211\u4eec\u53d1\u73b0\u5728\u63a5\u53d7TBI\u7684CB1R\u6572\u9664\u5c0f\u9f20\u4e2d\uff0cJZL184\u672a\u80fd\u907f\u514dTBI\u5f15\u53d1\u7684\u7a7a\u95f4\u5b66\u4e60\u548c\u8bb0\u5fc6\u969c\u788d\u4ee5\u53ca\u795e\u7ecf\u75c5\u7406\u5b66\u53d8\u5316\uff0c\u5305\u62ecTDP-43\u3001\u78f7\u9178\u5316tau\u548c\u7a81\u89e6\u6807\u8bb0\u7269PSD-95\uff08\u56fe6C\u548cD\uff09\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0cMAGL\u5931\u6d3b\u4ea7\u751f\u7684\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\u4e3b\u8981\u662f\u901a\u8fc7\u589e\u5f3a2-AG\u4fe1\u53f7\u4f20\u5bfc\uff0c\u4ece\u800c\u6fc0\u6d3b\u4e0b\u6e38\u7684CB1R\u4ecb\u5bfc\u7684\u4fe1\u53f7\u901a\u8def\u5b9e\u73b0\u7684\u3002<\/p>\n

    9.\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684 PPAR\u03b3 \u5728\u521b\u4f24\u6027\u8111\u635f\u4f24\u4e2d\u4ecb\u5bfc 2-AG \u4ea7\u751f\u7684\u795e\u7ecf\u4fdd\u62a4\u4f5c\u7528<\/h2>\n

    \u76ee\u524d\u5c1a\u672a\u8fdb\u884c\u7814\u7a76\u6765\u89e3\u6790\u5728\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2dMAGL\u5931\u6d3b\u4ea7\u751f\u7684TBI\u6709\u76ca\u6548\u5e94\u7684\u4e0b\u6e38\u4fe1\u53f7\u901a\u8def\u3002\u4ee5\u524d\u7684\u7814\u7a76\u8868\u660e\uff0c2-AG\u4fe1\u53f7\u8bf1\u5bfc\u7684\u6297\u708e\u6548\u5e94\u662f\u901a\u8fc7\u523a\u6fc0PPARc\u7684\u6d3b\u6027\u548c\u8868\u8fbe\u6765\u4ecb\u5bfc\u7684\uff0cPPARc\u901a\u8fc7\u6291\u5236NF-jB\u7684\u6d3b\u6027\u6765\u6291\u5236\u708e\u75c7\u76f8\u5173\u57fa\u56e0\u7684\u8868\u8fbe\uff0c\u800cNF-jB\u662f\u8c03\u63a7\u708e\u75c7\u76f8\u5173\u57fa\u56e0\u8868\u8fbe\u7684\u91cd\u8981\u8f6c\u5f55\u56e0\u5b50\u3002\u9274\u4e8ePPARc\u4e0eNF-jB\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u5728\u63a7\u5236\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf\u7684\u795e\u7ecf\u708e\u75c7\u4e2d\u8d77\u7740\u91cd\u8981\u4f5c\u7528\uff0c\u7814\u7a76\u4eba\u5458\u5047\u8bbePPARc\u5728\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u4f5c\u4e3a2-AG-CB1R\u4ecb\u5bfc\u7684\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\u7684\u4e0b\u6e38\u4fe1\u53f7\u5206\u5b50\u3002\u4e3a\u4e86\u6d4b\u8bd5\u8fd9\u4e00\u5047\u8bbe\uff0c\u7814\u7a76\u4eba\u5458\u9996\u5148\u8bc4\u4f30\u4e862-AG\u662f\u5426\u589e\u52a0\u4e86PPARc\u7684\u6d3b\u6027\uff0c\u5e76\u786e\u5b9a\u8be5\u6d3b\u6027\u662f\u5426\u53ef\u4ee5\u88abCB1R\u548cPPARc\u62ee\u6297\u5242\u963b\u65ad\u3002\u6b64\u5916\uff0c\u7814\u7a76\u4eba\u5458\u8fd8\u4f7f\u752815d-PGJ2\u4f5c\u4e3a\u5185\u6e90\u6027PPARc\u6fc0\u52a8\u5242\u8fdb\u884c\u4e86\u9633\u6027\u5bf9\u7167\u3002\u7ed3\u679c\u663e\u793a\uff0c2-AG\u663e\u8457\u63d0\u9ad8\u4e86PPARc\u8367\u5149\u7d20\u9176\u6d3b\u6027\uff0c\u800c\u8fd9\u79cd\u589e\u52a0\u53ef\u4ee5\u88abrimonabant\uff08\u4e00\u79cd\u6709\u6548\u4e14\u9009\u62e9\u6027\u7684CB1R\u62ee\u6297\u5242\uff09\u6216GW9662\uff08\u4e00\u79cdPPARc\u62ee\u6297\u5242\uff09\u963b\u65ad\u3002\u7136\u800c\uff0c15d-PGJ2\u8bf1\u5bfc\u7684PPARc\u8367\u5149\u7d20\u9176\u6d3b\u6027\u4e0d\u53d7rimonabant\u7684\u5f71\u54cd\uff0c\u4f46\u53ef\u4ee5\u88abGW9662\u963b\u65ad\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0c2-AG\u901a\u8fc7CB1R\u4ecb\u5bfc\u589e\u52a0\u4e86PPARc\u6d3b\u6027\u3002\u63a5\u4e0b\u6765\uff0c\u7814\u7a76\u4eba\u5458\u786e\u5b9a\u4e86TBI\u662f\u5426\u5bfc\u81f4\u4e86PPARc\u7684\u4e0b\u8c03\u4ee5\u53caNF-jB\u7684\u78f7\u9178\u5316\uff08p-NF-jB\uff09\u7684\u589e\u52a0\uff0c\u4ee5\u53ca\u8fd9\u4e9b\u6548\u5e94\u662f\u5426\u53ef\u4ee5\u901a\u8fc7\u589e\u5f3a2-AG\u4fe1\u53f7\u4f20\u5bfc\u901a\u8fc7\u836f\u7269\u6291\u5236MAGL\u6765\u64a4\u9500\u3002\u7ed3\u679c\u663e\u793a\uff0cTBI\u5bfc\u81f4\u4e86\u91ce\u751f\u578b\u5c0f\u9f20\u6d77\u9a6c\u4e2dPPARc\u8868\u8fbe\u7684\u51cf\u5c11\u548cp-NF-jB\u7684\u589e\u52a0\u3002\u7136\u800c\uff0c\u4f7f\u7528JZL184\u6cbb\u7597\u540e\uff0c\u8fd9\u4e9b\u53d8\u5316\u51cf\u8f7b\u6216\u51cf\u5f31\uff0c\u8fd9\u8868\u660e\u589e\u5f3a2-AG\u4fe1\u53f7\u4f20\u5bfc\u53ef\u4ee5\u51cf\u8f7bTBI\u5f15\u53d1\u7684PPARc\u4e0b\u8c03\uff0c\u4ece\u800c\u63d0\u9ad8p-NF-jB\u7684\u8868\u8fbe\u3002\u4e0e\u9884\u671f\u4e00\u6837\uff0c\u8fd9\u4e9bJZL184\u5bf9PPARc\u548cp-NF-jB\u7684\u5f71\u54cd\u5728CB1KO\u5c0f\u9f20\u4e2d\u6ca1\u6709\u89c2\u5bdf\u5230\u3002\u4e3a\u4e86\u786e\u8ba4MAGL\u5931\u6d3b\u5bfc\u81f4\u7684TBI\u4e2dPPARc\u548cp-NF-jB\u7684\u53d8\u5316\uff0c\u7814\u7a76\u4eba\u5458\u5728MAGL\u6572\u9664\u5c0f\u9f20\u4e2d\u8bc4\u4f30\u4e86PPARc\u548cp-NF-jB\u3002\u7ed3\u679c\u663e\u793a\uff0c\u91cd\u590d\u7684mCHI\u663e\u8457\u964d\u4f4e\u4e86\u91ce\u751f\u578b\u5c0f\u9f20\u7684\u6d77\u9a6c\u4e2dPPARc\u7684\u8868\u8fbe\uff0c\u5e76\u589e\u52a0\u4e86p-NF-jB\u7684\u8868\u8fbe\u3002\u7136\u800c\uff0c\u5728tKO\u548caKO\u5c0f\u9f20\u4e2d\uff0c\u4f46\u4e0d\u5728nKO\u5c0f\u9f20\u4e2d\uff0cTBI\u5f15\u53d1\u7684PPARc\u51cf\u5c11\u548cNF-jB\u589e\u52a0\u88ab\u51cf\u8f7b\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0c\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u964d\u89e3\u901a\u8fc7\u4e0b\u8c03PPARc\u548c\u4e0a\u8c03p-NF-jB\u4fc3\u8fdb\u4e86TBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u5b66\u53d8\u5316\uff0c\u63d0\u793a\u589e\u5f3a\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u76842-AG\u4fe1\u53f7\u4f20\u5bfc\uff0c\u800c\u4e0d\u662f\u795e\u7ecf\u5143\u4e2d\u7684\u4fe1\u53f7\u4f20\u5bfc\uff0c\u53ef\u4ee5\u9884\u9632\u8fd9\u4e9bTBI\u5f15\u53d1\u7684\u53d8\u5316\u3002 \u5982\u679c\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684PPARc\u662f\u4ecb\u5bfcMAGL\u5931\u6d3b\u5f15\u8d77\u7684TBI\u4e2d\u661f\u5f62\u80f6\u8d28\u7ec6\u80de2-AG\u4fe1\u53f7\u4ea7\u751f\u7684\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\u7684\u91cd\u8981\u4e0b\u6e38\u4fe1\u53f7\u5206\u5b50\uff0c\u90a3\u4e48\u5728aKO\u5c0f\u9f20\u4e2d\u9759\u9ed8PPARc\u7684\u4f5c\u7528\u5e94\u8be5\u6d88\u9664\u6216\u51cf\u8f7b\u5bf9\u8111\u5916\u4f24\u7684\u4fdd\u62a4\u4f5c\u7528\u3002\u4e3a\u4e86\u6d4b\u8bd5\u8fd9\u4e00\u5047\u8bbe\uff0c\u7814\u7a76\u4eba\u5458\u4f7f\u7528AAV\u8f7d\u4f53\u4ecb\u5bfc\u7684\u57fa\u56e0\u6c89\u9ed8\u6280\u672f\uff0c\u5728aKO\u5c0f\u9f20\u4e2d\u7279\u5f02\u6027\u9759\u9ed8\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684PPARc\u3002\u7ed3\u679c\u663e\u793a\uff0c\u5728\u63a5\u53d7AAV5-GFAP-eGFP-m-PPARc-shRNA\u8f7d\u4f53\u6ce8\u5c04\u7684aKO\u5c0f\u9f20\u4e2d\uff0cTBI\u540e\u7684TDP-43\u3001p-tau\u6216p-NF-jB\u4e4b\u95f4\u6ca1\u6709\u663e\u8457\u5dee\u5f02\uff0c\u4f46\u5728\u63a5\u53d7AAV-PPARc-shRNA\u8f7d\u4f53\u6ce8\u5c04\u7684aKO\u5c0f\u9f20\u4e2d\uff0cTBI\u540eTDP-43\u3001p-tau\u548cp-NF-jB\u663e\u8457\u589e\u52a0\u3002\u540c\u6837\uff0c\u5728\u63a5\u53d7AAV\u63a7\u5236\u8f7d\u4f53\u7684aKO\u5c0f\u9f20\u4e2d\uff0cTBI\u5e76\u6ca1\u6709\u663e\u8457\u964d\u4f4ePSD-95\u7684\u8868\u8fbe\u3002\u7136\u800c\uff0c\u5c06PPARc\u5728\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u6c89\u9ed8\u540e\uff0cTBI\u663e\u8457\u964d\u4f4e\u4e86PSD-95\u7684\u8868\u8fbe\u3002\u91cd\u8981\u7684\u662f\uff0c\u901a\u8fc7\u9759\u9ed8\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684PPARc\uff0c\u6d88\u9664\u4e86aKO\u5c0f\u9f20\u4e2dTBI\u5f15\u53d1\u7684\u7a7a\u95f4\u5b66\u4e60\u548c\u8bb0\u5fc6\u969c\u788d\u7684\u51cf\u8f7b\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0c\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u7684MAGL\u5931\u6d3b\u4ea7\u751f\u7684TBI\u4e2d\u7684\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\u53ef\u80fd\u4e3b\u8981\u901a\u8fc72-AG-CB1R-PPARc\u4fe1\u53f7\u4f20\u5bfc\u4ecb\u5bfc\u3002 \u4e3a\u4e86\u786e\u8ba4PPARc\u4f5c\u4e3a\u661f\u5f62\u80f6\u8d28\u7ec6\u80de2-AG\u4fe1\u53f7\u4ecb\u5bfc\u7684TBI\u4e2d\u795e\u7ecf\u4fdd\u62a4\u6548\u5e94\u7684\u91cd\u8981\u4e0b\u6e38\u4fe1\u53f7\u5206\u5b50\uff0c\u7814\u7a76\u4eba\u5458\u4f7f\u7528AAV5-GFAP-h-PPARc-FLAG-WPRE\u8f7d\u4f53\u5728\u91ce\u751f\u578b\u5c0f\u9f20\u7684\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2d\u8fc7\u8868\u8fbe\u4eba\u7c7bPPARc\u3002\u7ed3\u679c\u663e\u793a\uff0c\u5728\u63a5\u53d7AAV\u63a7\u5236\u8f7d\u4f53\u6cbb\u7597\u7684\u91ce\u751f\u578b\u5c0f\u9f20\u4e2d\uff0cTBI\u663e\u8457\u589e\u52a0\u4e86TDP-43\u3001p-tau\u548cp-NF-jB\uff0c\u5e76\u964d\u4f4e\u4e86PSD-95\u7684\u8868\u8fbe\u3002\u7136\u800c\uff0c\u5728\u8fc7\u8868\u8fbe\u661f\u5f62\u80f6\u8d28\u7ec6\u80de\u4e2dPPARc\u7684\u91ce\u751f\u578b\u5c0f\u9f20\u4e2d\uff0cTBI\u5f15\u53d1\u7684\u795e\u7ecf\u75c5\u7406\u5b66\u53d8\u5316\u5f97\u5230\u7f13\u89e3\uff0c\u5e76\u4e14TBI\u4e0d\u4f1a\u663e\u8457\u964d\u4f4e\u8fd9\u4e9b\u5c0f\u9f20\u7684\u8ba4\u77e5\u529f\u80fd\u3002\u8fd9\u4e9b\u6570\u636e\u63d0\u4f9b\u4e86\u8bc1\u636e\uff0c\u8868\u660ePPARc\u5145\u5f53\u4e86\u4e00\u4e2a\u91cd\u8981\u7684\u4e0b\u6e38\u4fe1\u53f7\u5206\u5b50\u3002<\/p>\n","protected":false},"excerpt":{"rendered":"

    Title: Enhancing endocannabinoid signalling in astrocyt […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1,23],"tags":[],"topics":[],"_links":{"self":[{"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/posts\/451"}],"collection":[{"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/comments?post=451"}],"version-history":[{"count":2,"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/posts\/451\/revisions"}],"predecessor-version":[{"id":511,"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/posts\/451\/revisions\/511"}],"wp:attachment":[{"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/media?parent=451"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/categories?post=451"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/tags?post=451"},{"taxonomy":"topics","embeddable":true,"href":"https:\/\/blog.ineuro.net\/index.php\/wp-json\/wp\/v2\/topics?post=451"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}