miR-195-5p调节TGF-β1/Smad3信号通路对心力衰竭大鼠心肌细胞的影响

Effects of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure through regulating TGF-β1/Smad3 signaling pathway

[目的]观察miR-195-5p调节TGF-β1/Smad3信号通路对心力衰竭(HF)大鼠心肌细胞的影响。[方法]将80只SD大鼠随机分为对照组、HF组、miR-195-5p-agomir组、miR-NC组,每组各20只,阿霉素建立HF大鼠模型。比较心功能、心肌细胞miR-195-5p表达、心肌细胞凋亡及凋亡相关蛋白、TGF-β1和Smad3表达。[结果]与对照组(0.82±0.22)比较,HF组(0.43±0.18)和miR-NC组(0.45±0.17)心肌细胞miR-195-5p相对表达量显著降低,miR-195-5p-agomir组(0.88±0.15)显著增加(P<0.05);与对照组比较,HF组左心室舒张末期内径(LVEDD)和左心室收缩末期内径(LVESD)显著增加,左心室射血分数(LVEF)显著降低,心肌细胞凋亡率和Bax蛋白表达水平显著升高,Bcl-2蛋白表达水平显著降低,TGF-β1和Smad3蛋白表达水平显著升高(P<0.05);与HF组比较,miR-195-5p-agomir组LVEDD和LVESD显著减小,LVEF显著增加,心肌细胞凋亡率和Bax蛋白表达水平显著降低,Bcl-2蛋白表达水平显著升高,TGF-β1和Smad3蛋白表达水平显著降低(P<0.05)。[结论]miR-195-5p在HF大鼠心肌细胞表达下调,过表达可通过调节TGF-β1/Smad3信号通路,抑制心肌细胞凋亡,改善心功能。

[Objective]To investigate the effects of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure(HF)through regulating TGF-β1/Smad3 signaling pathway.[Method]A total of 80 SD rats were randomly divided into control group,HF group,miR-195-5p-agomir group,miR-NC group,each with 20 rats.HF model was established using adriamycin.Thereafter various indexes were compared among four groups,including cardiac function indexes,expression of miR-195-5p in myocardial cell,apoptosis rate of myocardial cell,the expression levels of apoptosis related protein,TGF-β1 and Smad3.[Result]The relative expression of miR-195-5p in myocardial cell was(0.82±0.22)in control group,which was significantly higher than that in HF group(0.43±0.18)and miR-NC group(0.45±0.17),and was significantly lower than that of miR-195-5p-agomir group(0.88±0.15),with significant difference(all P<0.05);Compared with control group,there was a significant increase in left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),myocardial cell apoptosis rate and the expression levels of Bax,TGF-β1 and Smad3 in HF group,and a significant decrease in left ventricular ejection fraction(LVEF)and Bcl-2 protein expression levels in HF group(P<0.05);Compared with HF group,there was an significant increase in LVEDD,LVESD,myocardial cell apoptosis rate and the expression levels of Bax,TGF-β1 and Smad3 in miR-195-5p-agomir group,and an significant increase in LVEF and Bcl-2 protein expression levels in miR-195-5p-agomir group(P<0.05).[Conclusion]The expression of miR-195-5p is down-regulated in cardiomyocytes of HF rats,while the overexpression of miR-195-5p can inhibit cardiomyocyte apoptosis and improve cardiac function by regulating the TGF-β1/Smad3 signaling pathway.