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(0.75mg/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、CHIPmRNA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。
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 (P0.05). Meanwhile, MG-132 markedly elevated the mRNA and protein levels of Hsp70 and CHIP (P0.05). CONCLUSION: MG-132 protects myocardium against acute myocardial ischemia injury by inducing CHIP and Hsp70 expression.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2010年第7期747-752,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics