项目名称： 生地大黄汤通过HMGB1/TLR4/MMP-9信号通路保护急性脑出血时血脑屏障的机制研究

项目编号： No.81503555

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 俞晓飞

作者单位： 上海中医药大学

项目金额： 18万元

中文摘要： 急性脑出血严重威胁人类生命健康，脑出血时保护血脑屏障对维持神经元生存微环境稳态极其重要。前期研究证实生地大黄汤治疗急性脑出血临床疗效明确，能保护血脑屏障，减轻脑水肿，降低MMP-9表达和活性。生地大黄汤如何调控MMP-9表达，保护血脑屏障的作用机制须进一步明确。本项目结合HMGB1/TLR4/MMP-9信号通路激活在血脑屏障破坏中起重要作用的的新认识，提出“生地大黄汤通过干预HMGB1/TLR4/MMP-9信号通路保护急性脑出血时血脑屏障”的假说。拟分别采用体内动物模型（自发性高血压大鼠脑出血模型）及体外细胞模型（HMGB1诱导星型胶质细胞模型），明确急性脑出血时HMGB1/TLR4/MMP-9信号通路分子表达变化与血脑屏障破坏程度相关性及生地大黄汤通过HMGB1/TLR4/MMP-9信号通路保护血脑屏障的作用机制，为古方生地大黄汤治疗急性脑出血提供理论支持和依据。

中文关键词： 生地大黄汤；脑出血；血脑屏障；HMGB1/TLR4/MMP-9信号通路

英文摘要： Acute intracerebral hemorrhage seriously threats human’s life and heath. Protecting blood-brain barrier during ICH is extremely important to maintain steady state of the survival micro environment of neurons. Results of our studies showed that Rehmannia and Rhubarb Decoction had curative effect on ICH, it protected blood-brain barrier, reduced cerebral edema and depressed the expression and activity of MMP-9. However, the mechanisms of rehmannia and rhubarb decoction how to regulate the expression of MMP-9 and protect blood-brain barrier are unknown. In this project, we hypothesize that during ICH Rehmannia and Rhubarb Decoction protects blood-brain barrier through HMGB1/TLR4/MMP-9 signaling pathway basing on the new knowledge that the activation of this signaling pathway plays an important role to damage blood-brain barrier. We hope to find the changes of molecular expression in HMGB1/TLR4/MMP-9 signaling pathway during ICH and the correlation between the changes and the degree of blood-brain barrier damage, and to prove the mechanisms of Rehmannia and Rhubarb Decoction protecting blood-brain barrier through HMGB1/TLR4/MMP-9 signaling pathway in vivo（ICH model of spontaneous hypertensive rats）and in vitro（HMGB1 induced model of astrocytes）. This study will provide a theoretical support and basis for the use of Rehmannia and Rhubarb Decoction, a famous ancient prescription, to treat ICH.

英文关键词： Rehmannia and Rhubarb Decoction;Intracerebral Hemorrhage;Blood-brain Barrier;HMGB1/TLR4/MMP-9 Signaling Pathway