比索洛尔对高血压左室肥大大鼠心肌细胞GRK2表达的影响

Effects of Bisoprolol on Expression of GRK2 in Cardiac Myocytes of Hypertrophic Ventricle

目的观察比索洛尔对大鼠肥大心肌细胞G蛋白受体激酶2(GRK2)的影响,探讨比索洛尔改善心肌重塑的可能机制。方法以自发性高血压心力衰竭大鼠(SHR)为研究对象,通过免疫荧光标记、共聚焦显微镜及Werstern Blot等方法,检测比索洛尔干预后SHR左心室心肌细胞中GRK2的表达及其分布。结果心肌总蛋白中GRK2表达6月龄SHR组和WKY组比较无明显变化(60.7±1.9,62.1±2.2,P>0.05),8月龄SHR比6月龄SHR显著增加(78.5±2.1,60.7±1.9,P<0.05),均有心肌细胞膜上的聚积,8月龄SHR药物组比非药物组显著减少(65.9±2.2,78.5±2.1,P<0.05),心肌细胞膜上聚积减少。结论在心肌肥大的过程中,GRK2表达增加且有心肌细胞膜(闰盘)上的聚积,说明GRK2与心肌肥大关系密切,参与心肌肥大细胞信号途径的调控;比索洛尔抑制心肌细胞GRK2的表达以及细胞膜上的聚积,提示改善心肌肥大细胞信号途径的调控可能是比索洛尔逆转心脏重塑的机制之一。

Objective To investigate the effects of bisoprolol on GRK2 in the pathogenesis of hypertensive ventricle hypertrophy. Methods The expression and subcellular localization of GRK2 in the cardiac myocytes of left ventricle were determined by immuno-fluorescent labeling,confocal microscopy,and Western Blotting in 8 month old spontaneously hypertensive heart failure rats (SHR)fed with bisoprolol 2.5 mg/(kg·d)from 6 month old.Results There was no obvious difference of GRK2 expression be-tween 6 month old SHR and WKY rats (60.7±1.9,62.1±2.2,P>0.05).But the expression of GRK2 in 8 month old SHHF rats was increased in comparison with that both 6 month old SHR (78.5±2.1,60.7±1.9,P<0.01)and 8 month old SHHF rats fed with bisoprolol (65.9±2.2 vs 78.5±2.1,P<0.01).Membrane translocation of GRK2 was increased in 6,8 month old SHHF rats,but decreased in 8 month old SHR fed with bisoprolol.Conclusion GRK2 might play a role in the cell signaling transduction leading to cardiac hypertrophy.One of mechanisms in bisoprolol improving cardiac remodeling might inhibit the expression and mem-brane translocation of GRK2 in the cardiac myocytes.