蛋白酶体抑制剂MG-132对心肌梗死大鼠早期心功能及热休克蛋白70、热休克蛋白70羧基端相互作用蛋白的影响

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (7): 747-752.

蛋白酶体抑制剂MG-132对心肌梗死大鼠早期心功能及热休克蛋白70、热休克蛋白70羧基端相互作用蛋白的影响

张新民¹, 戴翠莲², 唐疾飞¹, 杨鹏麟¹

¹温州医学院附属第二医院心内科,温州 325000,浙江;
²遵义医学院附属医院心内科,遵义 563003,贵州

收稿日期:2010-01-11 修回日期:2010-04-29 出版日期:2010-07-26 发布日期:2020-09-15
通讯作者: 戴翠莲,女,博士,主任医师,研究方向:泛素蛋白酶体系统与心血管疾病。Tel: 13885238985 E-mail: daicuilian@yahoo.com.cn
作者简介:张新民,男,硕士,医师,研究方向:泛素蛋白酶体系统与心血管疾病。Tel : 13587644278 E-mail: zhxinming@163.com

Effects of proteasome inhibitor MG-132 on cardiac function and expressions of Hsp70 and CHIP in myocardial infarction rats

ZHANG Xin-min¹, DAI Cui-lian², TANG Ji-fei¹, YANG Peng-lin¹

¹Department of Cardiology, the Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang, China;
²Department of Cardiology, the Affiliated Hospital of Zunyi Medical College, Zunyi 563003, Guizhou, China

Received:2010-01-11 Revised:2010-04-29 Online:2010-07-26 Published:2020-09-15

摘要/Abstract

摘要： 目的: 研究蛋白酶体抑制剂MG-132对心肌梗死大鼠心脏结构、功能的影响及其分子机制。方法: 建立大鼠心肌梗死模型,干预组静脉注射MG-132(0.75 mg/kg),对照组及假手术组注射生理盐水,观察各组大鼠心脏心肌结构、功能及心肌热休克蛋白70(Hsp70)、热休克蛋白70羧基端相互作用蛋白(CHIP)的变化。结果: 与心梗对照组比较,MG-132干预组心肌坏死减少,左室舒张末压和血清脑钠肽水平减低(P<0.01),同时心肌组织Hsp70、CHIP mRNA和蛋白质表达水平显著升高(P<0.05)。结论: 蛋白酶体抑制剂MG-132能够减轻心肌梗死、改善心功能,其机制与上调Hsp70、CHIP水平有关。

关键词: 蛋白酶体抑制剂, 热休克蛋白, 热休克蛋白70羧基端相互作用蛋白, 心肌梗死

Abstract: AIM: The study was designed to examine the effect of proteasome inhibitor MG-132 on cardiac structure and function in myocardial infarction rats, and to investigate its mechanism. METHODS: The myocardial infarction model was established by ligating rat's left anterior descending coronary artery. Proteasome inhibitor MG-132 was administered in a dose of 0.75 mg·kg^-1·d^-1 for 7 days. The myocardial pathological change, infraction volume, hemodynamics and brian natriuretic peptide were measured to evaluate the cardiac function; realtime PCR and Western blotting were applied to measure the mRNA and protein expressions of Hsp70 and CHIP. RESULTS: MG-132 decreased the levels of myocardial infraction volume, left ventricular end diastolic presssure and serum BNP (P<0.05). Meanwhile, MG-132 markedly elevated the mRNA and protein levels of Hsp70 and CHIP (P<0.05). CONCLUSION: MG-132 protects myocardium against acute myocardial ischemia injury by inducing CHIP and Hsp70 expression.

Key words: Proteasome inhibitor, Heat shock proteins, Carboxyl terminus of the Hsc70-interacting protein, Myocardial infarction

中图分类号:

R965.2

张新民, 戴翠莲, 唐疾飞, 杨鹏麟. 蛋白酶体抑制剂MG-132对心肌梗死大鼠早期心功能及热休克蛋白70、热休克蛋白70羧基端相互作用蛋白的影响[J]. 中国临床药理学与治疗学, 2010, 15(7): 747-752.

ZHANG Xin-min, DAI Cui-lian, TANG Ji-fei, YANG Peng-lin. Effects of proteasome inhibitor MG-132 on cardiac function and expressions of Hsp70 and CHIP in myocardial infarction rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(7): 747-752.

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