脑出血后血管新生及中医药的作用机制研究.ppt

衡阳 2015.07 脑出血后血管新生 及中医药的作用机制研究 中南大学 中西医结合研究所 背 景 1）流行病学资料 ICH 13% SAH 13% Lacunar 19% Other 3% Unknown 32% Ischemic 71% Hemorrhagic 26% Cardioembolic 14% Thromboembolic 6% 欧美的数据 Up to 65,000 ICH per year in U.S. NINCDS Stroke Data Bank: Foulkes, Stroke, 1988； Yang QD, et al. Cerebrovasc Dis 2004，17: 303–313 中国的数据 ■ 脑出血占脑卒中的32.6% ■长沙的社区资料则达55.4% 2) 前期基础 新药开发： 脑溢安颗粒（ICH急性期） 脑溢安2号（ICH恢复期） 天龙熄风颗粒（缺血性中风急性期） 国家自然科学基金项目“脑溢安对出血性中风大鼠脑缺血损伤的保护作用研究” 国家自然基金青年项目“出血性中风大鼠神经胶质反应及中药干 预的研究” iNOS in astrocyte HO-1 in Microglia 国家自然科学基金项目“从神经干细胞分化角度探讨脑溢安对脑出血的脑保护机制” （编号 脑出血对微血管损伤 ■ 原发于血肿的机械性破坏 ■ 继发于炎症介导的损伤 研究的思路 微血管对脑的重要性 脑是血流高度依赖性器官 有利于维持脑内微环境的稳定 ■ 血脑屏障的组成 ■ 物质交换: 血氧的输运, 废物的清除 ■ 外周干预手段到达损伤部位的基本途径： 药物，细胞移植、各种修饰载体 微血管系统重建是脑组织修复、神经元抗损伤的必须过程 Luo EH, et al. Nat Rev Neurosci, 2003, 4: 399-415. Wei L, et al. Pathophysiology, 2005, 12:47-62. Change of mirovessels around and in the hematoma. No hemorrhage was found in sham control group (A). In ICH group, there was a hematoma in the right basal ganglion (inlet of panel B); no vessels were observed around and in the clot before 4?days (B), but many enlarged and thin-walled mirovessels (arrow) appeared close to the clot at 7?days (C) and extended into it from 14?days (D) then almost spread all over the clot at about 21?days (E). Dash lines marked the border of hematoma, and solid lines marked the border of the area where few vessels invaded in the hematoma. HE stain was used. Scale bars, 100?μm, 1?mm for the inlets. 血肿区有血管新生 研究内容 研究脑出血后血管新生的调控机制 Thrombin-induced angiogenesis following ICH Angiogenesis via VEGFR2 after ICH 从微血管系统重建的角度，以益气活血经典方－补阳还五汤和电针足三里为干预手段，探讨中医治疗脑出血的机制 结 果 1. Thrombin-induced angiogenesis following ICH Proliferated cerebral endothelial cells after ICH. A and B: Many BrdU-positive nuclei (arrows showing brown spots) in vWF-positive dilated vessels (blue) around the hematoma. C: Labeled nuclei in vessels increased until Day 14 after ICH. However, hirudin reduced