长期糖尿病大鼠心脏β肾上腺素受体及其亚型的改变

Alterations of cardiac β-adrenoceptor and its subtypes in long-term diabetic rats

目的：观察长期糖尿病大鼠心脏β肾上腺素受体（β－ＡＲ）及其亚型的改变。方法：链脲佐菌素（ＳＴＺ）诱导糖尿病大鼠动物模型，用放射配体结合实验和离体左心房收缩功能实验。结果：糖尿病大鼠心脏β－ＡＲ的最大结合容量下降３４％（Ｐ＜００５），ＫＤ值不变。ＣＧＰ２０７１２Ａ竞争抑制曲线两位点分析显示β１－和β２－ＡＲ之间比例未发生改变。糖尿病组异丙肾上腺素（ｉｓｏｐｒｏｔｅｒｅｎｏｌ，ＩＳＯ）激动β－ＡＲ介导的最大收缩反应（Ｒｍａｘ）较对照组下降６４％（Ｐ＜００５），ｐＤ２值显著增大（Ｐ＜００５），ＣＧＰ２０７１２Ａ阻断β１－ＡＲ后，β２－ＡＲ介导心肌的Ｒｍａｘ不变，而ｐＤ２值显著高于对照组（Ｐ＜００５）；ＩＣＩ１１８５５１阻断β２－ＡＲ后，β１－ＡＲ介导心肌的Ｒｍａｘ显著低于对照组（Ｐ＜００５），ｐＤ２值与对照组相比无显著差异。结论：长期糖尿病大鼠心脏β－ＡＲ总数明显下调，且β１－和β２－ＡＲ下调的程度相同；β－ＡＲ对ＩＳＯ敏感性的增加，主要是由β２－ＡＲ的改变引起，β－ＡＲ介导的最大收缩反应的降低，是由β１－ＡＲ的改变引起。

AIM and METHODS:The alterations of cardiac β-adrenoceptor(β-AR)and its subtypes in strepotozocin-induced diabetes mellitus rats were studied by radioligand binding assays,functional determination of isolated elective field driven left atria.RESULTS:β-AR density was decreased by 34%( P <0 05) in diabetic rat.Two sites analysis of CGP20712A competitive inhibition curves indicated that the ratio of two β-AR subtypes was not significantly changed.The maximum positive inotropic response(Rmax) induced by isoproterenol was decreased by 64%( P <0 05),and the pD 2 value was increased significantly in diabetic rat( P <0 05).After blocking β 1-AR with CGP20712A,the Rmax was not changed,the pD 2 value was significantly increased in diabetic rat.While after blocking β 2-AR with ICI118551,the pD 2 value was not altered,the Rmax was decreased significantly.CONCLUSONS:In long-term diabetic rats cardiac β-AR was significantly downregulated,with the same degree for the β 1-and β 2-AR.Rmax mediated by β-AR is reduced but the sensitivity to isoproterenol is increased,which is induced by alterations of β 1-AR and β 2-AR,respectively.