Rho/Rho激酶信号通路在异丙肾上腺素诱导的大鼠心肌重构中的作用

Effects of Rho/Rho kinase signaling on ventricular remodeling induced by isoprenaline in rats

目的:探讨Rho/Rho激酶信号通路在异丙肾上腺素诱导的大鼠心肌纤维化中的作用及机制。方法:24只雄性SD大鼠随机分成3组:空白对照组(对照组)、异丙肾上腺素模型组(模型组)、法舒地尔组。6周后测心脏重量指数(HWI),免疫组织化学检测心肌组织中转化生长因子-β1(TGF-β1)表达量,RT-PCR法检测心肌组织RhoA和Rho激酶mRNA的表达。结果:与模型组比较,法舒地尔组HWI下降(均P<0.05),TGF-β1、RhoA和Rho激酶mRNA表达减少(均P<0.01),但均高于对照组(均P<0.01)。结论:异丙肾上腺素诱导心肌纤维化伴有Rho/Rho激酶信号通路激活,Rho激酶抑制剂法舒地尔能抑制Rho/Rho激酶信号转导通路的活性、抑制TGF-β1表达,减轻心肌纤维化。

Objective： To investigate the effect of RhoA/Rho kinase signaling pathway on cardiac fibrosis induced by isoproterenol （ISO） in rats. Method： Twenty four SD rats were randomly divided into control group, ISO model group and Fasudil （Fas） group. After 6 weeks, the ratio of heart weight to body weight （HW/BW, HWI） was determined. Transforming growth factor β1 （TGF-β1） protein in myocardium was detected by immuno- histochemistry （IHC） staining. RhoA and Rho kinase mRNA were tested by RT-PCR. Result：The HWI, protein of TGF-β1, RhoA and Rho kinase mRNA were lower in Fas group than in ISO model group （P〈0.01）. Conclu- sion..Rho/Rho kinase signaling pathway may play an important role in myocardial fibrosis induced by ISO, and Fas, as Rho kinase inhibitor, can inhibit RhoA/Rho kinase signaling pathway and down-regulate TGF-β1 expres- sion.