Inhibition of endoplasm reticulum stress by ghrelin protects against ischemia/reperfusion injury in rat heart

被引：131

作者：

Zhang, Gai-Gai ^{[1
]}

Teng, Xu ^{[2
]}

Liu, Yue ^{[1
]}

Cai, Yan ^{[2
]}

Zhou, Ye-Bo ^{[2
]}

Duan, Xiao-Hui ^{[2
]}

Song, Jun-Qiu ^{[2
]}

Shi, Yi ^{[2
]}

Tang, Chao-Shu ^{[2
,3
,4
]}

Yin, Xin-Hua ^{[1
]}

Qi, Yong-Fen ^{[2
,3
,4
]}

机构：

[1] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin 150086, Peoples R China

[2] Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China

[3] Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China

[4] Peking Univ, Hosp 1, Inst Cardiovasc Dis, Beijing 100034, Peoples R China

来源：

PEPTIDES | 2009年 / 30卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Ghrelin; Ischemia/reperfusion injury; Endoplasmic reticulum stress; Apoptosis; Unfolded protein response; IN-VITRO; OXIDATIVE STRESS; ISCHEMIC-INJURY; PREVENTS; CARDIOMYOCYTES; ATTENUATION; DYSFUNCTION; MYOCARDIUM; ACTIVATION; APOPTOSIS;

D O I：

10.1016/j.peptides.2009.03.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Ghrelin is a multi-functional polypeptide with cardiovascular protective effects. We aimed to explore whether the cardioprotective effect of ghrelin is mediated by inhibiting myocardial endoplasmic reticulum stress (ERS). A Langendorff model of isolated rat heart was used with ischemia/reperfusion (I/R; 40/120 min). Cardiac function was monitored, and histomorphologic features, degree of myocardial injury, level of ERS markers, and number of apoptotic cardiomyocytes were determined. Compared with control group, the I/R group showed significantly decreased cardiac function, seriously damaged myocardial tissue, increased number of apoptotic cells, and overexpression of mRNA and protein of ERS markers. However, preadministration of ghrelin in vivo (10(-8) mol/kg, intraperitoneal injection, every 12 h, twice in all) greatly ameliorated the damaged heart function, attenuated myocardial injury and apoptosis, and decreased the expression of ERS markers: it decreased the mRNA and protein levels of glucose-regulated protein78 (GRP78) and C/EBP homologous protein (CHOP), with reduced caspase-12 protein expression. Furthermore, in vitro, ghrelin directly inhibited the myocardial ERS response induced by tunicamycin or dithiothreitol in rat cardiac tissue. Ghrelin could protect the heart against I/R injury, at least in part, through inhibiting myocardial ERS. (C) 2009 Published by Elsevier Inc.

引用

页码：1109 / 1116

页数：8

共 46 条

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