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|本期目录/Table of Contents|

促红细胞生成素衍生肽抑制细胞自噬减轻小鼠心肌缺血/再灌注损伤

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2016年第4期
页码:
390-395
栏目:
基础研究
出版日期:
2016-04-01

文章信息/Info

Title:
Helix B surface peptide attenuates myocardial ischemia/reperfusion injury by inhibiting autophagy
作者:
刘超权; 司 瑞; 宁明安; 刘立鹏; 胡建强; 张荣庆; 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):
LIU Chao-quan;  SI Rui;  NING Ming-an;  LIU Li-peng;  HU Jian-qiang;  ZHANG Rong-qing;  GUO Wen-yi
(Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
促红细胞生成素; 多肽; 缺血/再灌注; 小鼠; 自噬
Keywords:
erythropoietin;  polypeptide;  ischemia/reperfusion;  mouse;  autophagy
分类号:
R392.12
DOI:
-
文献标识码:
A
摘要:
目的 探讨促红细胞生成素衍生肽即螺旋B表面肽(helix B surface peptide,HBSP)对缺血/再灌注(I/R)诱导小鼠心肌细胞损伤的保护作用及其机制。方法 将56只雄性昆明小鼠随机分成4组：假手术(Sham)组、I/R组、I/R+HBSP组、I/R+HBSP+Wortmannin(I/R+HBSP+Wort)组。将原代心肌细胞随机分成4组：空白对照(Control)组、缺氧/复氧(H/R)组、H/R+HBSP组、H/R+HBSP+Wortmannin(H/R+HBSP+Wort)组。分别使用超声检测系统测定左室射血分数(LVEF)、左室短轴缩短率(FS)；双染法测定心肌梗死面积，Western blot检测蛋白表达及磷酸化水平，电镜观察细胞自噬小体及线粒体，共聚焦显微镜观察LC3(细胞自噬强度常用指标)数量。结果 与I/R组比较，I/R+HBSP组LVEF、左室FS增高(P<0.05)，心肌梗死面积缩小(P<0.05)，心肌细胞自噬小体数量减少。与I/R+HBSP组比较，I/R+HBSP+Wort组LVEF、左室FS下降(P<0.05)，心肌梗死面积增加(P<0.05)，心肌细胞自噬小体数量增加。与H/R组比较，H/R+HBSP组中p-Akt、p-mTOR及P62表达升高(P<0.05)，LC3-II/LC3-I比值下降(P<0.05)，LC3数量减少(P<0.05)。与H/R+HBSP组比较，H/R+ HBSP+Wort组中p-Akt、p-mTOR及P62表达下降(P<0.05)，LC3-II/LC3-I比值升高(P<0.05)，LC3数量增加(P<0.05)。结论 促红细胞生成素衍生肽能显著抑制细胞自噬减轻小鼠心肌I/R损伤，其保护效应可能与激活PI3K/Akt/mTOR转导通路相关。
Abstract:
AIM To investigate the protective effects and mechanisms of Helix B surface peptide (HBSP) against myocardial injury induced by ischemia/reperfusion in mice. METHODSMale mice (20±2 g) were randomly divided into four groups: sham group, ischemia/reperfusion group (I/R), I/R+HBSP group and I/R+HBSP+Wortmannin group (I/R+HBSP+Wort). Primary myocardial cells were randomly divided into four groups: control group, hypoxia/reoxygenation group (H/R), hypoxia/reoxygenation+HBSP group (H/R+HBSP) and hypoxia/reoxygenation+HBSP+Wortmannin group (H/R+HBSP+Wort). Cardiac functions and myocardial infarct size were evaluated. Autophagy and mitochondrion of cardiomyocytes were observed by transmission electron microscope. Expression of protein was detected by Western blotting and LC3 dots were calculated by confocal laser scanning microscope. RESULTSCompared with those in I/R group, the values of LVEF and FS in I/R+HBSP group were higher (P<0.05) and the values of myocardial infarct size and numbers of autophagy in I/R+HBSP group were reduced (P<0.05). Compared with those in I/R+HBSP group, LVEF and FS values in I/R+HBSP+Wort group were lower (P<0.05) and the values of myocardial infarct size and numbers of autophagy in I/R+HBSP+Wort group were increased (P<0.05). Compared with those in H/R group, expression of phosphor-Akt or phosphor-mTOR in H/R+HBSP group was higher (P<0.05) and LC3 dots in H/R+HBSP group were reduced (P<0.05). Compared with those in H/R+HBSP group, expression of phosphor-Akt or phosphor-mTOR in H/R+HBSP+Wort group was lower (P<0.05) and LC3 dots in H/R+HBSP+Wort group were increased (P<0.05). CONCLUSIONHelix B surface peptide attenuates myocardial ischemia/reperfusion injury by inhibiting autophagy. Its protective effect may be related to the activation of PI3K/Akt/mTOR signal pathway.

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备注/Memo

备注/Memo:
收稿日期：2015-07-30.
基金项目：国家自然科学青年资金项目资助（81200100）
通讯作者：郭文怡，主任医师,主要从事冠心病治疗研究 Email:guowenyi@tom.com
作者简介：刘超权，硕士生 Email:2209514494@qq.com
更新日期/Last Update: 2016-04-01