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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2016年第3期

页码:

268-272

栏目:

基础研究

出版日期:

2016-01-05

文章信息/Info

Title:

Melatonin ameliorates myocardial ischemia/reperfusion injury by reducing endoplasmic reticulum stress

作者:

于立明¹; 张秋芳²; 王晓武¹; 王 云³; 金振晓¹; 段维勋¹; 俞世强¹

（1.第四军医大学西京医院心血管外科，陕西 西安 710032；
2.西安市第四人民医院影像科，陕西 西安 710004；
3.宁夏医科大学附属医院心血管外科，宁夏 银川 750004）

Author(s):

YU Li-ming¹;  ZHANG Qiu-fang²;  WANG Xiao-wu¹;  WANG Yun³;  JIN Zhen-xiao¹;  DUAN Wei-xun¹;  YU Shi-qiang¹

(1.Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 710032, Xi’an 710032, Shaanxi, China；
2.Department of Radiology, Fourth Hospital, 710004, Xi’an 710004, Shaanxi, China；
3.Department of Cardiovascular Surgery, Affiliated Hospital, Ningxia Medical University, Yinchuan 750004, Ningxia, China)

关键词:

褪黑素; 心肌缺血再灌注损伤; 内质网应激; 心肌保护; 凋亡

Keywords:

melatonin;  myocardial ischemia/reperfusion injury;  endoplasmic reticulum stress;  cardioprotection;  apoptosis

分类号:

Q57

DOI:

-

文献标识码:

A

摘要:

目的 研究褪黑素（melatonin，Mel）对大鼠心肌缺血/再灌注（MI/R）损伤的预防作用与心肌内质网应激（endoplasmic reticulum stress,ER stress）水平变化情况。方法 90只体质量180~220 g雄性SD大鼠，随机分为3个组：假手术（Sham）组、溶剂对照（MI/R+V）组、Mel预防（MI/R+Mel）组。结扎大鼠左冠状动脉前降支30min后松开结扎线恢复血流灌注，建立MI/R损伤模型，再灌注4 h后Western blot法检测ER stress水平标志分子葡萄糖调节蛋白78（glucose regulated protein78,GRP78）及CCAAT/增强子结合蛋白同源蛋白（CCAAT/enhancer-binding protein homologous protein,CHOP）和凋亡相关蛋白表达情况；再灌6 h后ELISA法检测血清酶学指标，TUNEL法检测心肌细胞凋亡率，Evans blue-TTC双染法测定梗死面积；再灌注24 h后检测各大鼠超声心动图。结果 Mel预防性治疗4周可提高左室射血分数（LVEF）及左室短轴缩短率（LVFS），降低血清乳酸脱氢酶（LDH）及血清肌酸激酶（CK）水平，下调心肌细胞凋亡率及梗死面积，降低ER stress标志蛋白GGRP78及CHOP，降低凋亡通路蛋白（均P<0.01）。结论 Mel预防性治疗显著减轻心肌缺血再灌注损伤，其机制可能与抑制ER stress相关。

Abstract:

AIM To evaluate the protective action of melatonin (Mel) against myocardial ischemia/reperfusion (MI/R) injury and its association with endoplasmic reticulum stress (ER stress) level. METHODSNinety male Sprague Dawley rats (180-220 g) were subjected to myocardial ischemia/reperfusion (MI/R, I 30 min, R 6 h) operation by occluding the left descending artery and were randomly divided into three groups: MI/R+V (absolute alcohol diluted in sterile saline to 0.1 mol/L, 1 ml/d, 7 d before MI/R; 1 ml/d, 15 min before reperfusion, ip.), MI/R+Mel ［10 mg/(kg·d), 4 weeks before MI/R］ and sham (rats undergoing the same surgical procedures without tying the suture). After the 4-h reperfusion, ER stress marker GRP78 (glucose regulated protein78), CHOP (CCAAT/enhancer-binding protein homologous protein) and apoptosis-related protein were measured. After the 6-h reperfusion, serum LDH and CK levels, apoptotic index and infarct size were detected. After the 24-h reperfusion, cardiac functions were evaluated. RESULTSRats treated with Mel for 4 weeks showed markedly improved cardiac functions, lower serum LDH and CK level, decreased apoptotic index, reduced infarct size, down-regulated GRP78 and CHOP expressions and decreased apoptosis-related protein expressions (all P<0.01). CONCLUSIONMelatonin treatment ameliorates MI/R injury by reducing ER stress, thus improving post-MI/R cardiac functional recovery.

参考文献/References

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备注/Memo

备注/Memo:

收稿日期：2015-05-14.
基金项目：国家十二五学科支撑计划项目资助（2011BAI11B20）；国家自然科学基金项目资助（81470415、81470411）；陕西省自然科学基金项目资助（2014JM4106）；西京医院学科助推计划项目资助（XJZT14203）
通讯作者：俞世强，主任医师，主要从事心脏微创研究 Email：shiqiangyu210@126.com 共同
通讯作者：段维勋，主治医师，主要从事抗心肌缺血/再灌注损伤基础与临床研究 Email：duanweixun@126.com
作者简介：于立明，博士生 Email：lmyu2012@163.com

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更新日期/Last Update: 2016-01-07