17β-雌二醇对体外机械牵张诱导心肌细胞肥大的影响

The effect of 17β-estradiol on mechanical stretch-induced hypertrophy of cultured cardiomyocyte

目的:研究17β-雌二醇(17β-estradiol,E2)对体外机械牵张诱导的心肌细胞肥大的影响。方法:以机械牵张刺激体外培养的新生大鼠心肌细胞,建立心肌细胞肥大模型,采用免疫荧光方法分析心肌细胞表面积、Western blot方法检测肥大指标之一β-MHC的表达,以观察E2对机械牵张诱导的心肌细胞肥大的影响,并采用Western blot方法检测心肌细胞整合素β1(inte-grinβ1)表达的变化。结果:与对照组相比,机械牵张24 h后,心肌细胞表面积、心肌细胞胎儿型蛋白β-MHC表达增加,表明机械牵张24 h可诱导心肌细胞肥大。同时,机械牵张24 h心肌细胞整合素β1水平亦显著增加。100 nmol/L E2预处理30 min可明显减轻机械牵张诱导的心肌细胞表面积和β-MHC蛋白水平的增加,降低机械牵张诱导的心肌细胞整合素β1增加,该效应可被雌激素受体非特异性拮抗剂ICI182780逆转。结论:一定水平的E2可改善机械牵张诱导的心肌细胞肥大反应,并且能降低机械牵张诱导的integrinβ1表达的增加。

Objective：To investigate the effect of 17β-estradiol（E2） on cultured cardiomyocyte hypertrophy induced by mechanical stretch.Methods：Cardiomyocytes from neonatal rats were cultured in vitro and cardiomyocyte hypertrophy was induced by mechanical stretch.The effect of E2 on cardiomyocyte hypertrophy was evaluated by the surface areas of cardiomyocytes using immunocytochmistry and the β-MHC protein levels detected by Western blot.The integrin β1 protein levels were determined by Western blot.Results：Mechanical stretch for 24 h significantly increased cell surface areas and β-MHC protein levels,which suggested that mechanical stretch is a direct stimulus for isolated cardiomyocytes to develop hypertrophy.Mechanical stretch also significantly increased the expression of integrin β1 protein in cultured cardiomyocytes.Pretreatment with 100 nmol/L E2 for 30 min significantly attenuated the increases in cell surface areas and β-MHC protein levels induced by mechanical stretch which were attenuated by estrogen receptor antagonist ICI182780.Furthermore,E2 also decreased the levels of integrin β1 protein induced by mechanical stretch,and this was also attenuated by ICI182780.Conclusion：E2 prevents cardiomyocyte hypertrophy and the increase of integrin β1 protein induced by mechanical stretch in vitro.