转化生长因子β_1在心衰大鼠心肌中的表达及氟伐他汀对其的调节作用

Regulation of Fluvastatin on the Expression of Myocardial TGF-β_1 in Rats with Heart Failure after Acute Myocardial Infarction

目的研究转化生长因子β1(TGF-β1)在心肌梗死后心衰大鼠心肌中的表达及羟甲基戊二酰辅酶A(3-hy-droxyl-3-methylglutaryl coenzyme A,HMG-CoA)还原酶抑制剂氟伐他汀对其的调节作用。方法雌性SD大鼠急性心肌梗死(AMI)术后6 h随机分为:①AMI对照组;②氟伐他汀组;另设:③假手术组。直接灌胃给药8周后行高频多普勒超声、血流动力学、心脏重塑指标、左室非梗死区心肌TGF-β1mRNA和蛋白免疫印迹测定。结果与假手术组比较,AMI对照组左室舒张末期内径(LVEDD)、左室舒张末期容积(LVEDV)、E峰、E峰减速度、E/A、左室舒张末压(LV-EDP)、左、右心室心肌肥厚指数、非梗死区胶原容积分数(CVF)、TGF-β1mRNA及蛋白表达均显著增加(均P<0.01),左室短轴缩短率(FS)和射血分数(EF)均显著降低(均P<0.01)。与AMI对照组比较,氟伐他汀组的LVEDD、LV-EDV、E峰、E峰减速度、E/A、LVEDP、左、右心室心肌肥厚指数、CVF、TGF-β1mRNA和蛋白表达均显著降低(均P<0.01),FS和EF显著升高(均P<0.01)。结论氟伐他汀能有效抑制心室重塑,延缓心衰进展,其机制可能部分通过下调心肌梗死后心衰大鼠心肌TGF-β1的表达,改善炎症反应。

Objective To investigate the expression of left ventricular （LV） myocardial transforming growth factor β1 （TGF-β1） in rats with heart failure after acute myocardial infarction （AMI） and its modulation by fluvastatin （FV）. Methods Six h after establishment of AMI model, the femal SD rats were randomly assigned to： AMI control group and AMI＋FV group, and sham-operated group was selected randomly as non infarction control. After 8 weeks of treatment with drugs by gastric gavage, cardiac function, hemodynamics, ventricular remodeling parameters, TGF-β1 mRNA and protein expression in LV noninfarcted area （NIA） were measured. Results As compared with sham-operated group, LV end-diastolic dimension （LVEDD）, LV end diastolic volume （LVEDV）, E wave, E-wave deceleration, E/A ratio, LV end diastolic pressure （LVEDP）, relative weight （LVRW）, right ventricular relative weight （RVRW）, collagen volume fraction （CVF） and TGF-β1 mRNA and protein in NIA were all significantly increased in AMI group （all P〈0.01）, while fractional shortening （FS） and ejection fraction （EF） were significantly decreased （all P〈0.01）. In comparison with AMI group, LVEDD, LVEDV, E-wave, E-wave deceleration, E/A, LVEDP, LVRW, RVRW, CVF and TGF-β1 mRNA and protein in NIA were all significantly decreased （all P〈0.01）, while FS and EF were significantly increased in FV group （both P〈0.01）. Conclusion FV can attenuate LV remodeling and heart failure after AMI in rats, partly through down-regulating the expression of TGF-β1 and improving inflammatory response.