微小RNA-208a-3p通过靶向GATA4的表达对小鼠心肌梗死后心肌肥厚的影响及其机制  

Effect of Micro-RNA-208a-3p on Myocardial Hypertrophy after Myocardial Infarction by Targeting GATA4 Expression and Its Mechanism in Mice

作　　者：侯光强[1] 柏勇 HOU Guangqiang;BAI Yong(Department of Cardiology,Guangyuan Mental Health Center,Guangyuan,Sichuan 628000,China)

机构地区：[1]广元市精神卫生中心心血管内科,四川广元628000

出　　处：《岭南心血管病杂志》2024年第2期214-218,234,共6页South China Journal of Cardiovascular Diseases

摘　　要：目的探究微小RNA(microRNA,miR)-208a-3p通过靶向GATA4的表达对小鼠心肌梗死(myocardial infarction,MI)后心肌肥厚(cardiac hypertrophy,CH)的影响和机制。方法小鼠分为对照组、MI组、MI+miR-208a-3p抑制剂组(n=12)。通过结扎构建CH模型,静脉注射miR-208a-3p抑制剂(300μg)以抑制miR-208a-3p的水平。4周后测量小鼠心脏质量(mg)与胫骨长度(mm)比值评估CH情况。通过苏木素伊红染色检测心肌组织的病理变化。检测心肌组织中miR-208a-3p和GATA4表达水平。双荧光素酶报告基因测定评估靶向关系。并检测过表达miR-208a-3p对心肌细胞中GATA4表达的影响。结果MI组小鼠的miR-208a-3p水平、心脏质量与胫骨长度比值、心肌细胞表面积显著高于对照组,GATA4 mRNA和蛋白水平显著低于对照组,差异有统计学意义(P<0.05)。MI+miR-208a-3p抑制剂组的miR-208a-3p水平、心脏质量与胫骨长度比值、心肌细胞表面积显著低于MI组,GATA4 mRNA和蛋白水平显著高于MI组,差异有统计学意义(P<0.05)。miR-208a-3p与GATA4 mRNA在心肌细胞中靶向结合,并且过表达miR-208a-3p显著抑制心肌细胞中GATA4 mRNA和蛋白表达(P<0.05)。结论MI后miR-208a-3p的升高通过靶向抑制GATA4的表达诱发CH。Objectives To explore the effect and mechanism of microRNA(miR)-208a-3p on cardiac hypertrophy(CH)after myocardial infarction(MI)by targeting GATA4 expression in mice.Methods Mice were divided into control group,MI group,MI+miR-208a-3p inhibitor group(n=12).CH model was built by ligation.MiR-208a-3p was inhibited by intravenous injection of miR-208a-3p inhibitor(300μg).Heart mass(HM,mg)/tibia length(TL,mm)were measured after 4 weeks to assess CH.The pathological changes of myocardial tissue were detected by hematoxylin eosin(HE)staining.The expression levels of miR-208a-3p and GATA4 in myocardial tissue were detected.Dual-luciferase reporter was applied to assess targeting relationships.The effect of over expression of miR-208a-3p on GATA4 expression in cardiomyocytes was detected.Results The level of miR-208a-3p,HW/TL,and myocardial cell surface area in MI group were significantly higher than those in control group,and the levels of GATA4 mRNA and protein were significantly lower than those in control group(P<0.05).The level of miR-208a-3p,HW/TL,and myocardial cell surface area in MI+miR-208a-3p inhibitor group were significantly lower than those in MI group,and the GATA4 mRNA and protein levels were significantly higher than those in MI group(P<0.05).There was targeted binding of miR-208a-3p to GATA4 mRNA in cardiomyocytes.Over expression of miR-208a-3p significantly inhibited the expression of GATA4 mRNA and protein in cardiomyocytes(P<0.05).Conclusions Elevation of miR-208a-3p after MI induces CH through targeted inhibition of GATA4 expression.

关 键 词：心肌梗死 心肌肥厚 miR-208a-3p GATA4 

分 类 号：R542.22[医药卫生—心血管疾病]