心肌细胞自噬在尿毒症心肌病中的作用及其分子机制研究

目的：探讨尿毒症时心肌细胞是否存在自噬现象、自噬与尿毒症小鼠心肌病发生发展的关系及尿毒症时心肌细胞自噬可能的细胞内信号调控机理。方法建立小鼠尿毒症心肌病动物模型，于建模12周后处死小鼠取心脏标本，通过透射电镜观察心肌组织中的自噬体，并采用免疫组织化学染色及蛋白印记法（Western-blot）检测心肌细胞自噬及自噬相关蛋白的表达情况。结果造模组小鼠12周后透视电镜下观察到心肌组织中具有双层膜结构的自噬体，免疫组织化学染色显示心肌细胞 Ubiquitin、Cathepsin-D、Rab 7表达尿毒症小鼠较对照组明显增强。尿毒症小鼠心肌组织中自噬相关基因 LC-3、Beclin-1，相关细胞因子表达较对照组明显增强。结论心肌细胞自噬与尿毒症小鼠心功能改变密切相关。

The effect and molecular mechanism of cardiac myocytes autophagy in uremia cardiomyopathy

Objective This study will focus on revealing the phenomenon of cardiac myocytes autophagy in uremic cardiomyopathy and the relevance with occurrence and development in mouse uremic cardiomyopathy. Clarify the occurrence of cardiac myocytes autophagy in uremia and their intracellular signal regulatory mechanism. Methods Establish 5/6 mice uremic cardiomyopathy model, collect blood and heart tissue, observe the autophagosome by transmission electron microscopy, count the positive cells and caculate the percentage of cardiac myocytes by HE and immunohistochemistrical staining, detect inflammatory factors and autophagy associated protein by ELISA and Western method. Results Autophagosome is abserved by transmission electron microscop. Immunohistochemical dye show that the express of Ubiquitin, Cathepsin-D,Rab 7 enhanced in uremia mice cardiac myocytes compared with control group. In uremia mice heart tissue ,autophagy associated gene LC-3,Beclin-1expressed enhanced compared with control group. Conclusion Our study indicate the presence of autophagy in uremia mice cardiac myocytes,and cardiac myocytes autophagy have close relation to heart dysfunction in uremia mice.