星形胶质细胞Connexin43在大脑皮层梗死继发丘脑变性中的作用及机制研究

项目名称： 星形胶质细胞Connexin43在大脑皮层梗死继发丘脑变性中的作用及机制研究

项目编号： No.81501952

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： 左夏林

作者单位： 广州医科大学

项目金额： 18万元

中文摘要： 目前对脑皮层梗死后继发丘脑变性的机制尚未完全阐明，多认为与轴突退行性改变、神经营养障碍、氧化损伤等因素有关。但原发灶损伤的神经细胞是如何介导下级神经细胞受损仍不清楚。而Connexin43(Cx43)作为连接相邻细胞的通道蛋白，在星形胶质细胞中大量表达，对小分子物质(如无机离子、ATP、葡萄糖等)在细胞间传递中发挥重要作用。有研究显示，星形胶质细胞中组织蛋白酶B(CathepsinB，CathB)在脑卒中后被激活，降解Cx43，阻碍ATP在细胞间的输送。但Cx43在脑皮层梗死后继发丘脑变性中的作用仍知之甚少。本课题拟制备大鼠大脑皮层梗死模型，探讨星形胶质细胞中CathB-Cx43途径在丘脑中对ATP输送的影响以及在神经元变性的作用；然后在体外细胞实验中进一步验证CathB-Cx43-ATP之间的调控机制。本研究有望进一步阐明脑梗死继发性损害的特点和机制，为有效防治继发性损害提供新的思路。

中文关键词： 星形胶质细胞；缝隙连接蛋白Cx43；脑梗死；；丘脑；继发变性

英文摘要： The mechanism of secondary damage after cortical infarction is not fully understood, many factors may be involved, such as axonal degeneration, neurotrophic disorders, inhibition of protein synthesis, oxidative damage and so on. The gap junction protein connexin43 (Cx43) is widely expressed in adult astrocytes and forms intercellular channels for the transfer of small molecules between the cytoplasm of adjacent cells. Many researches have showed that cathepsinB (CathB) degradation of Cx43 protein after focal cerebral ischemia, then preventing the formation of Cx43 channels. But the relationship between the CathB and Cx43 in the secondary damage after cortical infarction is not fully understood. In order to confirm the hypothesis that the CathB degradation of Cx43 protein and hinder the formation of Cx43 channels, causing extracellular ATP levels decreased, resulting in nerve cell damage in the secondary damage after cortical infarction. We intend to investigate the role of CathB-Cx43 in the secondary damage of thalamus after cortical infarction in rats and analyze the effect of Cx43 on extracellular ATP levels in vivo and in vitro. The research results will elucidate the mechanism of Cx43 on secondary damage in thalamus after cortical infarction through a new visual angle.

英文关键词： Astrocytes;Cx43;Cerebral infarction ;thalamus;Secondary damage