心肌肥厚大鼠心肌细胞变化与Cx43表达

Expression of connexin 43 and pathological changs of cardiomyocyte in myocardial hypertrophy rats

目的探讨异丙肾上腺素(isoproterenol,ISO)致心肌肥厚大鼠心肌细胞间隙连接蛋白43(connexin 43,Cx43)表达的变化。方法皮下注射,异丙肾上腺素4 mg/(kg.d),每日2次,连续5 d,建立大鼠心肌肥厚模型(ISO组),观察大鼠体重(mB)、心脏重量(mH)和左心室重量(mLV),心肌细胞横径(transdiameter of cardiomyocyte,TDM)和心肌细胞截面积(cardiomyocyte area,CA),苏木素伊红(HE)染色观察细胞病理学改变,免疫组化染色和蛋白印记(western blotting)方法观察心肌细胞Cx 43的变化。结果与对照组比较,ISO组大鼠mH/mB、mLV/mB、TDM和CA明显增加(P<0.05,P<0.01);心肌细胞病理学显示,ISO组心肌纤维走向紊乱,细胞大小不均,较对照组心肌细胞变大,密度变小;免疫组化结果表明,对照组大鼠心肌细胞Cx 43颗粒典型地排列在心肌闰盘处,ISO组心肌细胞Cx 43颗粒发生重排,杂乱分布于闰盘、心肌细胞膜各部位和胞浆内;蛋白印记法结果显示,ISO组Cx 43表达量明显低于对照组。结论异丙肾上腺素致心肌肥厚导致Cx 43蛋白表达改变,加速间隙连接降解和功能异常。

Objective To study the expression of connexin 43 gap junction protein of cardiomyocytes in ventricular hypertrophy rats induced by isoproterenol（ISO）.Methods Myocardial hypertrophy model of rat was induced by injection of ISO 4 mg（1kg·d）,two times a day for 5 days.Body,heart,and left ventricular mass of the rats were weighted.Transdiameter of cardiomyocyte（TDM） and cardiomyocyte area（CA） were measured under microscope.Pathological changes in cardiomyocytes with HE staining were observed.The expression of connexin 43 in cardiomyocytes was measured using immunocytochemistry and western bloting.Results Compared with the control group,the ratio of heart mass/body mass,left ventricular mass/body mass,TDM,and CA increased markedly（P0.05,P0.01）.The direction of myocardial fiber was disordered in ISO group.The cell size was unequal and cell density became lower than that of the control group.Immunolabeling of connexin 43 was confined to the intercalated disks in the normal ventricular myocytes of control rats.But hypertrophied cardiomyocytes of ISO rats showed dispersion of connexin 43 immunolabelled over the cell surface and in the cytoplasm.The result of western bloting showed decreased expression of connexin 43 in ISO group.Conclusion Myocardial hypertrophy induced by ISO is associated with the expression of connexin 43 and ISO accelerates gap junction degradation.