Ghrelin通过抑制ERS减轻ISO所致的心肌损伤和心肌细胞凋亡  

Ghrelin reduces isoproterenol-induced myocardial injury and cardiomyocyte apoptosis via inhibiting endoplasmic reticulum stress

作　　者：张改改 蔡怀秋[2] 张金胜[3] 宁明 吴扬 齐永芬[3] 尹新华[2] 

机构地区：[1]清华大学第一附属医院北京华信医院干部病房,北京100016 [2]哈尔滨医科大学第一附属医院心内科,黑龙江哈尔滨150086 [3]北京大学医学部教育部分子心血管病学重点实验室,北京100191

出　　处：《心脏杂志》2014年第3期249-253,共5页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(81000046)

摘　　要：目的:探讨ghrelin(G)减轻异丙基肾上腺素(isoproterenol,ISO)所致心肌损伤和凋亡是否与其抑制心肌内质网应激(endoplasmic reticulum stress,ERS)有关。方法:将29只雄性Sprague-Dawley(SD)大鼠随机分为对照(Con)组、ISO组和ISO+G组。Con组皮下注射生理盐水,ISO组皮下注射ISO,ISO+G组皮下注射ISO前2 d皮下注射ghrelin。采用生理记录仪测定各组大鼠心功能。以HE染色及血浆乳酸脱氢酶(LDH)及肌酸激酶MB(CK-MB)活性的测定评估心肌损伤的程度。用TUNEL法测定心肌细胞的凋亡。用Western blot检测各组心肌组织中ERS标志性分子C/EBP同源蛋白(C/EBP-homologous protein,CHOP)和caspase-12的表达。结果:外源性ghrelin可显著缓解ISO所致大鼠的心功能不全,减轻ISO造成的心肌损伤,减少心肌细胞凋亡,并降低CHOP和剪切的caspase-12的表达。结论:ghrelin通过抑制ERS可减轻ISO所致心肌损伤和心肌细胞凋亡。AIM： To investigate whether ghrelin （G）-reduced myocardial injury and cardiomyocyte ap optosis induced by isoproterenol （ISO） is related to the inhibition of endoplasmic reticulum stress （ERS）. METHODS： Twentynine male Sprague Dawley （SD） rats were randomly divided into control group （n =9）, ISO group （n = 11） and ISO ＋ G group （n =9）. Rats in control （Con） group were sub cutaneously injected with normal saline. Rats in ISO group were injected with ISO and rats in ISO ＋ G group were injected with ghrelin 2 days before injection of ISO. Hemodynamic parameters of the rats in each group were recorded by the Power Lab system. Myocardial tissue injury was assessed by HE staining and activity determination of plasma lactate dehydrogenase （LDH） and creatinine kinase （CK）MB. Cardiomyocyte apoptosis was detected by TUNEL method and the expression of ERS markers C/EBPho mologous protein （CHOP） and RESULTS ： Exogenous ghrelin cleaved caspase12 in myocardial tissue was detected by Western blot. alleviated heart dysfunction, reduced myocardial injury and cardiomyocyte apoptosis and inhibited overexpressions of CHOP and cleaved caspase-12. CONCLUSION： Ghrelin reduced ISO-induced myocardial injury and cardiomyocyte apoptosis via inhibiting ERS.

关 键 词：GHRELIN 异丙基肾上腺素 心肌疾病 内质网应激 凋亡 

分 类 号：Q25[生物学—细胞生物学]