异丙肾上腺素诱导的心功能不全中自噬的变化

doi:10.3969/j.issn.1006-7795.2016.06.001

首都医科大学学报 ›› 2016, Vol. 37 ›› Issue (6): 719-724.doi: 10.3969/j.issn.1006-7795.2016.06.001

• 心血管疾病的病理生理机制 • 上一篇下一篇

异丙肾上腺素诱导的心功能不全中自噬的变化

白燕^1,2, 徐文丽^1,2, 吕婷婷^1,2, 武烨^1,2, 王丽³, 王雯^1,2, 马新亮¹, 刘慧荣²

1. 首都医科大学基础医学院生理学与病理生理学系, 北京 100069;
2. 代谢紊乱相关心血管疾病北京市重点实验室, 北京 100069;
3. 山西医科大学病理教研室, 太原 030001

收稿日期:2016-10-03 出版日期:2016-12-21 发布日期:2016-12-16
通讯作者: 马新亮, 刘慧荣 E-mail:xin.ma@jefferson.edu;liuhr2000@126.com
基金资助:
国家自然科学基金（31401006），北京市自然科学基金重点项目（7151001），973计划前期研究专项（2014CB560704）。

Change of autophagy in the isoprenaline-induced cardiac dysfunction

Bai Yan^1,2, Xu Wenli^1,2, Lyu Tingting^1,2, Wu Ye^1,2, Wang Li³, Wang Wen^1,2, Ma Xinliang¹, Liu Huirong²

1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
2. Key Laboratory of Metabolic Disorders Related Cardiovascular Disease, Beijing 100069, China;
3. Department of Pathology, Shanxi Medical University, Taiyuan 030001, China

Received:2016-10-03 Online:2016-12-21 Published:2016-12-16
Supported by:
This study was supported by National Natural Science Foundation of China(31401006), Natural Science Foundation of Beijing (7151001),973 Special Preliminary Study Plan(2014CB560704).

摘要/Abstract

摘要： 目的探讨在异丙肾上腺素诱导的心功能不全中自噬的变化。方法用异丙肾上腺素腹腔注射法建立小鼠心功能不全模型；小动物超声影像系统检测心功能指标射血分数（ejection fraction，EF）、左室缩短率（fractional short，FS）、舒张早期充盈峰值/房缩期充盈峰值（ratio of early peak flow velocity and atrium peak flow velocity，E/A）和室间隔厚度（interventricular septum，IVS）的变化；尾压法间接检测血流动力学指标——心率（heart rate，HR）、收缩压（systolic blood pressure，SBP）、舒张压（diastolic blood pressure，DBP）和平均动脉压（mean blood pressure，MBP）的变化；心质量体质量比法即心脏质量（heart weight，HW）/体质量（body weight，BW）检测心脏质量指数的变化；Western blotting印迹法检测心脏组织中自噬标志物LC3、p62的变化。结果与对照组相比，异丙肾上腺素模型组在4周后，小鼠心功能下降，EF下降、FS下降、IVS增加，差异具有统计学意义；同时模型组小鼠HR和DBP低于对照组，差异具有统计学意义；心脏质量指数指标（HW/BW）显示模型组较对照组增高；自噬标志物检测显示，异丙肾上腺素注射1 d和3 d后，LC3Ⅱ/LC3Ⅰ比值升高，p62蛋白的相对量降低；连续注射4周后，LC3Ⅱ/LC3Ⅰ比值与p62蛋白的相对量恢复至对照组水平。结论异丙肾上腺素诱导的心功能不全过程中，心肌自噬早期升高，晚期恢复至正常水平。

关键词: 异丙肾上腺素, 心功能不全, 自噬

Abstract: Objective To observe the change of myocardial autophagy during the isoprenaline-induced mice cardiac dysfunction. Methods The mice model of cardiac dysfunction was established by intraperitoneal injection of isoprenaline persistently for 4 weeks. Cardiac function was monitored by ultrasonic imaging system; hemodynamic changes were measured via tail-cuff method; autophagy-related protein expressions of LC3Ⅱ/LC3Ⅰand p62 were detected by Western blotting. Results After treatment with isoprenaline for 4 weeks, ejection fraction and fractional short reduced, interventricular septum increased, the ratio of early peak flow velocity and atrium peak flow velocity (E/A) tended to be elevated, suggesting declined cardiac function in model group compared with control group. Correspondingly, the heart rate and diastolic blood pressure decreased in model group compared with control group. After the injection of isoprenaline for 1 day and 3 days, the level of LC3Ⅱ/LC3Ⅰincreased and relative expression of p62 increased, but both returned to normal levels at the 4th week. Conclusion In the progress of isoprenaline-induced cardiac dysfunction, myocardial autophagy increased at an early stage, then returned to the normal level appearing to be a dynamic trend.

Key words: isoprenaline, cardiac dysfunction, autophagy

中图分类号:

R541

白燕, 徐文丽, 吕婷婷, 武烨, 王丽, 王雯, 马新亮, 刘慧荣. 异丙肾上腺素诱导的心功能不全中自噬的变化[J]. 首都医科大学学报, 2016, 37(6): 719-724.

Bai Yan, Xu Wenli, Lyu Tingting, Wu Ye, Wang Li, Wang Wen, Ma Xinliang, Liu Huirong. Change of autophagy in the isoprenaline-induced cardiac dysfunction[J]. Journal of Capital Medical University, 2016, 37(6): 719-724.

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异丙肾上腺素诱导的心功能不全中自噬的变化

Change of autophagy in the isoprenaline-induced cardiac dysfunction

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