糖尿病减弱心肌组织肌浆网钙转运三磷酸腺苷酶的-国家心血管病中心.pdf

932 中国循环杂志 2014 年 11 月 第 29 卷 第 11 期（总第 197 期）Chinese Circulation Journal，November，2014，Vol. 29 No.11（Serial No.197） 基础与实验研究 糖尿病减弱心肌组织肌浆网钙转运三磷酸腺苷酶的小泛素样修饰 * 姚晶，邵兴慧，宋光远，赵振燕，高海洋，武德崴，滕思勇，吴永健 摘要 目的：探索糖尿病是否可以通过心肌组织肌浆网钙转运三磷酸腺苷 (ATP) 酶（SERCA2a）的小泛素样修饰进而影响 SERCA2a 的活性与表达。 方法：采用小动物超声和左心室压力测定评价 2 型糖尿病大鼠（糖尿病组）和对照大鼠（对照组）心肌收缩和舒张 功能；比较糖尿病组大鼠和对照组大鼠心肌组织内 SERCA2a 的表达情况，用免疫共沉淀方法以及小泛素样修饰试剂 盒比较糖尿病组大鼠和对照组大鼠心肌组织内 SERCA2a 小泛素样修饰程度。 结果：和对照组大鼠比较：糖尿病组大鼠心肌收缩、舒张功能均下降，尤以舒张功能下降更为明显；糖尿病组大 鼠心肌组织内 SERCA2a 蛋白水平、基因表达和小泛素样修饰程度均下降；小泛素样修饰 E2（Ubc9）的蛋白水平在糖 尿病大鼠心肌中也下降，而小泛素样蛋白 1（SUMO1）和小泛素样修饰 E1（SAE1 和 SAE2 组成的二聚体）蛋白水平无 明显变化。 结论：SERCA2a 小泛素样修饰程度和 Ubc9 蛋白水平在糖尿病心肌组织中下降，提示 SERCA2a 小泛素样修饰和 Ubc9 与糖尿病的心肌损伤密切相关。 关键词 糖尿病；肌浆网钙转运 ATP 酶；小泛素样修饰 Diabetes Reducing the Intensity of Sarcoplasmic Reticulum Ca2+-ATPase-SUMOylation of Myocardium in Experimental Rats YAO Jing, SHAO Xing-hui, SONG Guang-yuan, ZHAO Zhen-yan, GAO Hai-yang, WU De-wei, TENG Si-yong, WU Yong-jian. Department of Cardiology, Cardiovascular Institute and Fu Wai Hospital, CAMS and PUMC, Beijing (100037), China Corresponding Author: WU Yong-jian, Email: fuwaihospital@ Abstract Objective: To investigate the effect of diabetes on the intensity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a)- SUMOylation and SERCA2a activity of myocardium in experimental rats. Methods: The 8 weeks old SD rats were divided into 2 groups, Diabetic group, with diet-induced type 2 diabetic rats and Control group, with normal rats. The systolic and diastolic cardiac functions were evaluated by echocardiography and left ventricular pressure measurement. The intensity of SERCA2a-SUMOylation was examined by co-immunoprecipitation and SUMOylation kit. Results: Compared with Control group, Diabetic group had decreased systolic and diastolic cardiac func