同济大学学报（医学版）2018，Vol.39Issue(3)：24-29,6.DOI:10.16118/j.1008-0392.2018.03.005
单硝酸异山梨酯上调外泌体-microRNA378表达减轻机械牵张诱导的心力衰竭
Isosorbide mononitrate inhibits mechanical stress-induced heart failure through upregulating expression of exosomal-microRNA378
摘要
Abstract
Objective To investigate the effects of isosorbide mononitrate ( ISMN) on mechanical stress-induced heart failure and its relation to exosomal-microRNA378 ( miRNA378). Methods The pressure overload heart failure model in vivo and in vitro were induced by transverse aortic constriction ( TAC) in C57BL/6 mice for 4 weeks or by mechanical stretch on cultured cardiomyocytes for 48 h, respectively. Fifteen C57BL/6 male mice were divided into control group, ascending aortic constriction group ( TAC group ) and ascending aortic constriction+ISMN group ( TAC+ISMN group ) in vivo experiment. The cultured cardiomyocytes were divided into 5 groups: control group, stretch group, stretch+miRNA378 mimic group, stretch+ISMN group and stretch+ISMN+miRNA378 inhibitor group. The echocardiography, heart weight/body weight ratio (HW/BW), the morphology of cardiomyocyte, plasma NT-proBNP and the expression of exosomal-microRNA378 were examined for in vivo model. The cardiomyocytes were collected and the mRNA expression of atrial natriuretic peptide ( ANP) and skeletal-α-actin ( SAA ) was detected with RT-qPCR for in vitro model. Results In in vivo experiments, the LVIDd, LVAWd, HW/BW and plasma NT-proBNP levels in TAC+ISMN group were significantly lower than those in TAC group( P＜0.05) , FS in TAC+ISMN group was significantly higher than that in TAC group ( P＜0.05 ). RT-qPCR shows that the expression of exosomal-microRNA378 was significantly upregulated in TAC+ISMN group compared with TAC group ( P＜0. 05). In in vitro experiments, the expressions of ANP and SAA in cardiomyocytes were significantly decreased in stretch+ISMN group and stretch+microRNA378 mimic group compared with stretch group ( P＜0.05) , however, there were no significant differences between stretch+ISMN+microRNA378 inhibitor group and stretch group ( P＞0.05). Conclusion Isosorbide mononitrate inhibits mechanical stress-induced heart failure through upregulation of the exosomal-microRNA378 expression.关键词
单硝酸异山梨酯/外泌体-microRNA378/机械牵张/心力衰竭Key words
isosorbide mononitrate/exosomal-microRNA378/mechanical stress/heart failure分类
医药卫生引用本文复制引用
张卫君,刘琳琳,林利..单硝酸异山梨酯上调外泌体-microRNA378表达减轻机械牵张诱导的心力衰竭[J].同济大学学报（医学版）,2018,39(3):24-29,6.基金项目
国家自然科学基金(81570237) （81570237）
中国医师协会项目(DFCMDA201259) （DFCMDA201259）
