白细胞介素-6对人脑动静脉畸形细胞连接的影响及机制研究

IL-6和MMP-9在破裂脑动静脉畸形（cAVM）组织中的表达明显高于未破裂组且MMP-9能降解神经元细胞连接膜外蛋白部分；电镜示畸形组织细胞连接减少；肌动蛋白相关基因WASL在遗传性出血性毛细血管扩张症患者中下调，由此我们假设在cAVM细胞连接相关基因表达下调基础上IL-6可能通过某种MARK通路或氧化应激反应使细胞连接受损。为证实假设，我们在前期原代培养的cAVM内皮细胞模型基础上，用IL-6共培养畸形内皮细胞，加入各种丝裂原活化蛋白激酶信号通路（ERK,P38和JNK）的抑制剂，检测各组反应后的ERK,P38,JNK,MMP-9,细胞连接蛋白（VE-cadherin、cingulin,ZO）的表达以及细胞肌动蛋白和微管聚合反应，并用基因芯片测定AVM细胞连接和细胞骨架相关基因表达。检测患者手术前后时期血液中IL-6水平的变化。旨在为临床工作提供新的药物靶点及为畸形出血提供新的预警指标

IL-6 and MMP-9 expression of ruptured cerebral arteriovenous malformation in the tissues was significantly higher than the expression unruptured group; And MMP-9 was reported degrading membrane protein parts of cell junction of neurons. Thus we assume that IL-6 May through some MARK pathways or oxidative stress reaction makes cell membrane protein degradation of the connection in cells, microfilaments polymerization increase and the tube protein depolymerization increase.all these lead to cell connection damaged,thus cause blood vessels to instability. To prove this assumption we establish the primary cell line of the brain arteriovenous malformation endothelial cell model, with IL-6 cocultured, and on the basis of the original crack with various silk amp-activated protein kinase signal pathway (ERK, P38 and JNK) inhibitors, testing the reaction of after ERK, P38, JNK, MMP-9, cell connection protein (VE-cad herin, claudin, ZO-1) expression and cell actin and microtubules polymerization reaction, and gene chip method for determining arteriovenous malformation cell connection and cytoskeleton gene expression. Testing the plasma interleukin -6 level of cerebral arteriovenous malformation patients before and after surgery . Aims to show that basis on the influence of IL-6 and cytoskeleton gene downexpression,the stability fo endothelial cell wall of cerebal arteriovenous malformation , provide new targets for clinical treatment.