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|本期目录/Table of Contents|

mTOR信号介导的自噬在褪黑素减轻心脏缺血/再灌注损伤中的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第3期
页码:
249-253
栏目:
基础研究
出版日期:
2018-03-25

文章信息/Info

Title:
Role of mTOR-mediated autophagy in melatonin-alleviated myocardial ischemia reperfusion injury
作者:
徐臣年; 吕 涛; 李聪叶; 尉 迟; 闫浩东; 林 晨; 孙冬冬; 郭文怡
(第四军医大学西京医院心血管内科，陕西 西安 710032)
Author(s):
XU Chen-nian;  L? Tao;  LI Cong-ye;  WEI Chi;  YAN Hao-dong;  LIN Chen;  SUN Dong-dong;  GUO Wen-yi
(Department of Cardiology, Xijing Hospital, Fourth Military University, Xi’an 710032, Shaanxi, China)
关键词:
褪黑素; 自噬; mTOR; 缺血/再灌注; 心脏
Keywords:
melatonin;  autophagy;  mTOR;  ischemia reperfusion;  heart
分类号:
R743.35
DOI:
-
文献标识码:
A
摘要:
目的 探讨mTOR信号介导的自噬在褪黑素（melatonin,Mel）减轻心脏缺血/再灌注损伤中的作用。方法 将60只8周龄C57BL/6小鼠随机分为假手术（Sham）组、单纯褪黑素10 mg/(kg·d)处理(Mel)组、缺血/再灌注（ischemia reperfusion,I/R）组和褪黑素10 mg/(kg·d)干预I/R（Mel+I/R）组。采用冠状动脉左前降支结扎术制备心肌I/R模型，HE染色观察心肌组织形态学变化，试剂盒检测各组血清中LDH的含量，TUNEL染色检测各组细胞凋亡情况，蛋白印迹法（Western blot）检测自噬相关蛋白微管相关蛋白1轻链3（microtubule-associated protein 1 light chain 3,LC3）I和II、Beclin1和mTOR磷酸化的表达，免疫荧光染色法检测LC3B的表达。结果 与Sham组相比，Mel组各项指标均无明显变化；I/R组心肌纤维断裂明显排列紊乱，血清中LDH含量明显增加（P<0.01），TUNEL阳性细胞明显增多（P<0.01），LC3II和Beclin1表达显著升高（P<0.01），而磷酸化mTOR的表达降低（P<0.01），免疫荧光结果显示LC3B表达增加（P<0.01）； Mel+I/R组可明显减轻心肌纤维的断裂，降低血清中LDH含量（P<0.01），减少TUNEL阳性细胞数（P<0.01），减少LC3II和Beclin1的表达（P<0.01），降低免疫荧光染色中LC3B的表达（P<0.01）。结论 褪黑素通过调节mTOR信号介导的自噬减轻心脏I/R损伤。
Abstract:
AIM To investigate the role of mTOR-mediated autophagy in melatonin-alleviated myocardial ischemia reperfusion injury. METHODSMale C57BL/6 mice were randomly divided into four groups: sham (Sham) group, melatonin group ［10 mg/(kg·d)］ control (Mel) group, ischemia reperfusion (I/R) group and ischemia reperfusion plus melatonin ［10 mg/(kg·d)］ (Mel+I/R) group. Coronary artery left anterior descending artery ligation was used to prepare myocardial ischemia for 30 min and reperfusion for 4 h. The pathological morphological changes in the myocardial fiber were analyzed by HE staining. Lactate dehydrogenase content in serum was determined and myocardial cell apoptosis was tested with TUNEL method. The expressions of LC3I/II, Beclin1 and phosphorylation of mTOR were detected using Western blot and the expression of LC3B was detected using immunofluorescence staining. RESULTSNo significant differences were found in the parameters detected between Sham and Mel. I/R significantly increased the content of LDH (P<0.01), accompanied by the disordered arrangement of myocardial fibers, up-regulation of LC3II and Beclin1, increased myocardial apoptosis index, and down-regulation of p-mTOR (P<0.01). Immunofluorescence staining showed significantly increased expression of LC3B (P<0.01). These effects were significantly attenuated by melatonin (P<0.01). CONCLUSIONMelatonin can significantly reduce myocardial ischemia reperfusion injury by regulating mTOR-mediated autophagy.

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备注/Memo

备注/Memo:
收稿日期：2017-10-09.基金项目：国家自然科学基金项目资助（81770224） 通讯作者：郭文怡，教授，主要从事冠心病临床与基础机制研究 Email：guowenyi@tom.com 共同通讯作者：孙冬冬，副教授，主要从事糖尿病心肌病临床与基础机制研究 Email：51483696@qq.com 作者简介：徐臣年，硕士生 Email：1156489870@qq.com
更新日期/Last Update: 1900-01-01