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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Atorvastatin downregulates tissue plasminogen activator-aggravated genes mediating coagulation and vascular permeability in single cerebral endothelial cells captured by laser microdissection.
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Atorvastatin downregulates tissue plasminogen activator-aggravated genes mediating coagulation and vascular permeability in single cerebral endothelial cells captured by laser microdissection.

机译：阿托伐他汀下调组织纤溶酶原激活物加重的基因，介导激光显微切割捕获的单个脑内皮细胞的凝血和血管通透性。

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The effects of statins on gene expression of cerebral endothelial cells (ECs) in vivo have not been investigated after stroke. We developed a rapid double immunofluorescent staining protocol with antibodies against von Willebrand factor (a marker for endothelium) and glial fibrillary acidic protein (a marker for astrocytes) for laser capture microdissection to isolate single ECs in brain tissue of the rat. Using this protocol in combination with real-time PCR, we found that stroke significantly increased mRNA levels of protease-activated receptor 1 (PAR-1) and tissue factor (TF) in ECs isolated from ischemic cerebral microvessels compared with nonischemic vessels. Treatment of embolic stroke with recombinant human tissue plasminogen activator (rht-PA) 4 h after stroke further elevated PAR-1 mRNA levels nearly 1000-fold in the core and 500-fold in the boundary above the nonstroke group 30 h after stroke, while TF mRNA levels were elevated approximately 10 fold above the nonstroke group. Furthermore, stroke significantly increased matrix metalloproteinase (MMP) 2 and 9 mRNA levels in the ischemic core and boundary regions 6 and 30 h after stroke. Treatment with rht-PA-upregulated MMP2 expression in the ischemic boundary and core. Atorvastatin completely blocked rht-PA upregulation of the above genes, when atorvastatin in combination with rht-PA was administered 4 h after stroke. Monotherapy of atorvastatin 4 h after stroke did not significantly reduce expression of genes examined in the present study. These data provide evidence that atorvastatin reduces exogenous tPA-aggravated cerebral endothelial genes that mediate thrombosis and blood-brain barrier permeability, which could contribute to the beneficial effects of statins on thrombolytic treatment of acute stroke.
机译：中风后尚未研究他汀类药物对体内脑内皮细胞（EC）基因表达的影响。我们开发了一种快速双重免疫荧光染色方案，使用针对血管性血友病因子（内皮标记）和神经胶质纤维酸性蛋白（星形胶质细胞标记）的抗体进行激光捕获显微切割，以分离大鼠脑组织中的单个EC。使用此协议与实时PCR的组合，我们发现与非缺血性血管相比，中风显着增加了从缺血性脑微血管分离的EC中蛋白酶激活受体1（PAR-1）和组织因子（TF）的mRNA水平。脑卒中后30 h，重组人组织纤溶酶原激活剂（rht-PA）治疗栓塞性卒中，使非卒中组的PAR-1 mRNA水平在非卒中组的核心进一步升高了近1000倍，在边界处升高了500倍，而TF mRNA水平比非中风组高约10倍。此外，中风显着增加了中风后6小时和30小时的缺血性核心和边界区域的基质金属蛋白酶（MMP）2和9 mRNA水平。用rht-PA上调缺血边界和核心区MMP2的表达。当中风后4小时施用阿托伐他汀与rht-PA组合时，阿托伐他汀完全阻断了上述基因的rht-PA上调。脑卒中后4小时使用阿托伐他汀的单药治疗并未显着降低本研究中检测的基因表达。这些数据提供了阿托伐他汀减少介导血栓形成和血脑屏障通透性的外源性tPA加重的脑内皮基因的证据，这可能有助于他汀类药物对急性脑卒中的溶栓治疗的有益作用。

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