缺血性脑卒中是严重的脑血管疾病。脑缺血时，神经血管单元中的MMP/TIMP系统平衡被破坏，中性粒细胞、血管内皮细胞和神经元高表达MMP-9；随后星形胶质细胞、小胶质细胞和周细胞高表达MMP-2和MMP-3；高表达的MMPs继而活化和水解基膜蛋白，破坏血脑屏障，加剧中性粒细胞浸润以及诱导神经炎性反应和神经元损伤，使梗死面积不断扩大。因此，研究MMP-9抑制剂对于开发高效的抗缺血性脑卒中的药物具有非常重要的意义。.申请者的前期研究和文献调研表明，丹酚酸类化合物在体内外均具有明显的MMP-9抑制活性。本项目将在体内外评价一系列丹酚酸类化合物的MMP-9抑制作用，进行血脑屏障的保护作用和分子机制研究，并在整体动物水平对其脑缺血治疗的疗效进行确证，期待发现新型高效的抗脑卒中候选化合物。

Ischemic stroke is a sever cerebrovascular disease. On the initial of ischemic stroke, the MMP/TIMP balance was destroyed. First of all, MMP-9 was overexpression in neutrophil cells, vascular endothelial cells and neurons. Then MMP-2 and MMP-3 were overexpression in star glial cells and glial cells. The large amount of MMPs could further induce the hydrolysis of membrane protein, destroy the blood brain barrier, increase neutrophil cell infiltration and induce neuro-inflammation. As a results, the brain infarct area was significantly expanded. So it was of great significance to discover novel MMP-9 inhibitors for the treatment of ischemic stroke..Previous study and literature research showed that salvianolic acids could inhibit MMP-9 activity significantly both in vivo and in vitro. This project will evaluate the MMP-9 inhibitory effects of a series of salvianolic acids. After taking into consideration the pharmacokinetic properties, blood brain barrier protective effects and the action mechanism of these inhibitors, their therapeutic effects would be carefully confirmed on animal models in order to find a novel promising candidate compound on ischemic stroke.