头穴透刺调控RhoA-ROCK通路促进脑出血大鼠神经血管稳态重构的机制研究

项目名称： 头穴透刺调控RhoA-ROCK通路促进脑出血大鼠神经血管稳态重构的机制研究

项目编号： No.81202747

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 鲍春龄

作者单位： 上海中医药大学

项目金额： 23万元

中文摘要： 神经血管单元NVU是中风病新的研究焦点。脑出血后RhoA- ROCK信号被激活，导致NVU的各组分相互联系遭到破坏，因此使"神经血管稳态重构"关键治疗靶点。动态观察脑出血后神经行为学变化；透射电镜观察血肿周围组织NVU的病理变化；荧光显微镜观察Fluoro-jade C、OX-6染色后神经元变性、小胶质细胞激活情况；免疫组化、RT-PCR等检测血管内皮紧密连接(claudin-5、occludin、ZO-1)、神经再生 (NGF、GAP-43) 相关蛋白及其基因；分析与RhoA/ ROCK通路及其下游信号分子MLC/ F-actin的关系。证实头穴透刺能调控RhoA/ ROCK通路，改善微血管内皮细胞紧密连接，保护血脑屏障，减轻脑水肿和促进神经再生；与信号通路抑制剂比较，更具有靶向性。头穴透刺对NVU具有整体调节效应，神经血管稳态重构为整体研究神经元损伤及保护机制，寻找治疗的新靶点提供依据

中文关键词： 头穴；脑出血；Rho激酶；神经血管稳态；信号通路

英文摘要： NVU(neurovascular unit) is the new research focus of stroke. Rho/Rho-kinase signaling pathway plays a role of "molecular witch" ,after intracerebral hemorrhage， it damaged interconnection of NVU different structures, so Rho A -ROCK signaling pathway is the target for treatment. Observe rats' neurological behavior after cerebral hemorrhage continuously. Pathological changes of NVU around hematoma was observed By TEM. The neuron degeneration and microglia activation were observed after Fluoro-jade C staining or OX-6 staining respectively by fluorescence microscope. The expression of claudin-5,occludin,ZO-1 related to vascular endothelial permeability and the expression of NGF,GAP-43 related to neural regeneration were detected by immunohistochemistry. The genes content of the protein mentioned above were detected by RT-PCR. As the same time, analysis the correlation to RhoA/ ROCK. Confirm that scalp penetration acupuncture can regulates Rho/ Rock signaling pathway to improve TJ (tight junction) of microvascular endothelial cells,protect BBB(blood-brain barrier), reduce the degree of encephaledema, promote nerve regeneration. Compared with Fasudil, scalp penetration acupuncture had targeting effect significantly. Scalp penetration acupuncture has whole-regulation-effect, that reconstruct cerebral hemorrhage

英文关键词： scalp acupuncture；intracerebral hemorrhage；Rho associated kinase ;ROCK；neural-vascular steady-state；signaling pathway