溶酶体组织蛋白酶B参与细胞凋亡机制的研究

项目名称： 溶酶体组织蛋白酶B参与细胞凋亡机制的研究

项目编号： No.81460187

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李志刚

作者单位： 赣南医学院

项目金额： 47万元

中文摘要： 溶酶体可能是程序性细胞坏死、凋亡、自噬这三种程序性细胞死亡（PCD）信号通路网络的程序调控中心。本项目以研究溶酶体与凋亡信号通路的关系为突破口，作为我们系列研究的第一步。基于以往和我们的研究，我们推测cathepsin B可能是通过Rho/ROCK、JNK信号通路介导细胞凋亡。本课题拟利用相关特异性抑制剂对大鼠局灶性脑缺血再灌注模型进行干预，观察溶酶体超微结构的变化，检测脑梗死体积、凋亡细胞以及cathepsin B、caspases、Bcl-2家族蛋白和Rho/ROCK信号通路、JNK信号通路等相关蛋白的表达及其相互作用，从Rho/ROCK和JNK信号通路等方面探讨脑缺血再灌注溶酶体介导细胞凋亡的机制，以期进一步完善脑缺血再灌注溶酶体与PCD关系的理论机制，并为脑缺血再灌注PCD的防治探寻新的靶点。

中文关键词： 溶酶体；细胞凋亡；组织蛋白酶B；C-Jun；氨基末端激酶信号通路；Rho/Rho；激酶信号通路

英文摘要： Lysosomes may be a program control center of signal pathway network of necrotic PCD (programmed cell death,PCD),apoptotic PCD and autophagic PCD.This project is to study the relation of lysosomes and the signal path of apoptosis as the breakthrough point,which is the first step of our series of studies. Based on previous studies and our research,we assume that cathepsin B may be mediated apoptosis through Rho/ROCK (Rho kinase) and JNK signal pathway.The project is to observe the changes of ultrastructure of lysosomes and detect cerebral infarct volumes and apoptotic cells as well as the expressions and interactions between cathepsin B,caspases,Bcl-2 family proteins,and related proteins with Rho/ROCK and JNK signal pathway by means of the intervention in rat models of focal cerebral ischemia/reperfusion with related specific inhibitors.From the aspect of Rho/ROCK and JNK signal pathway,the project explores the mechanisms of apoptosis induced by lysosomes,and further improve the theoretical mechanism on the relationship between lysosomes and PCD,and search new targets for the prevention and treatment of PCD in cerebral ischemia/reperfusion injury.

英文关键词： Lysosomes;Apoptosis;Cathepsin B;JNK signal pathway;Rho/ROCK signal pathway