信号转导和转录激活因子3调控缺氧诱导丝裂原因子表达对心肌细胞肥大的影响

Effect of STAT3 regulating expression HIMF on cardiomyocyte hypertrophy

目的探讨信号转导和转录激活因子3(STAT3)对血管紧张素Ⅱ(AngⅡ)诱导的大鼠心肌细胞肥大及缺氧诱导丝裂原因子(HIMF)表达的影响。方法体外分离SD大鼠心肌细胞并进行培养,将大鼠心肌细胞分为对照组、AngⅡ组、AngⅡ+干扰RNA(siRNA)-阴性对照(NC)组、AngⅡ+siRNA-STAT3组、AngⅡ+siRNA-HIMF组(n=6),检测各组心肌细胞表面积、心房钠尿肽(ANP)、β肌球蛋白重链(β-MHC)、HIMF、STAT3蛋白表达水平。结果与对照组比较,AngⅡ组ANP、β-MHC、HIMF、磷酸化STAT3(p-STAT3)/STAT3蛋白表达水平明显升高(P<0.01)。AngⅡ+siRNA-STAT3组ANP、β-MHC、HIMF及p-STAT3/STAT3蛋白表达水平明显低于AngⅡ组和AngⅡ+siRNA-NC组(P<0.05)。AngⅡ组心肌细胞表面积明显高于对照组[(1024.33±85.46)μm;vs(451.76±50.35)μm^(2),P<0.05],AngⅡ+siRNA-STAT3组心肌细胞表面积明显低于AngⅡ+siRNA-NC组[(615.47±61.63)μm;vs(984.54±90.23)μm^(2),P<0.05]。AngⅡ+siRNA-HIMF组心肌细胞ANP、β-MHC、HIMF蛋白表达水平和心肌细胞表面积明显低于AngⅡ+siRNA-NC组(P<0.01)。结论抑制STAT3表达可通过调控HIMF表达进而抑制AngⅡ诱导的大鼠心肌细胞肥大。

Objective To investigate the effect of STAT3 on hypertrophy of rat cardiomyocytes induced by AngⅡand on expression of HIMF.Methods After SD rat cardiomyocytes were isolated and cultured,the cells were divided into control group,AngⅡgroup,AngⅡ+siRNA-NC group,AngⅡ+siRNA-STAT3 group and AngⅡ+siRNA-HIMF group(n=6).The myocardial cell surface area,ANP level were measured,and the protein expression levels ofβ-MHC,HIMF and STAT3 were detected in each group.Results The protein levels of ANP,β-MHC,HIMF and p-STAT3/STAT3 were significantly higher in AngⅡgroup than in control group(P<0.01).The above levels were notably lower in the cardiomyocytes from the AngⅡ+siRNA-STAT3 group than in AngⅡgroup and the AngⅡ+siRNA-NC group(P<0.05).The surface area of cardiomyocytes was statistically larger in AngⅡgroup than in control group(1024.33±85.46μm~2 vs 451.76±50.35μm~2,P<0.05),and was less in the AngⅡ+siRNA-STAT3 group than the AngⅡ+siRNA-NC group(615.47±61.63μm~2 vs 984.54±90.23μm~2,P<0.05).The expression levels of ANP,β-MHC and HIMF in cardiomyocytes and the surface area of cardiomyocytes were significantly lower in AngⅡ+siRNA-HIMF group than in AngⅡ+siRNA-NC group(P<0.01).Conclusion Suppression of STAT3 can inhibit AngⅡ-induced rat cardiomyocyte hypertrophy by regulating the HIMF expression.