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长期糖尿病大鼠心脏 肾上腺素受体及其亚型的改变 |
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宫海滨 韩启德
摘 要 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。
主题词 糖尿病；受体，肾上腺素能，β；心脏
Alterations of cardiac β－adrenoceptor and its subtypes in long-term diabetic rats
GONG Hai-Bin,HAN Qi-De
Institute of Vascular Medicine,Third Hospital,Beijing Medical University,Beijing(100083)
Abstract 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 pD2 value was increased significantly in diabetic rat(P＜0.05).After blocking β1－AR with CGP20712A,the Rmax was not changed,the pD2 value was significantly increased in diabetic rat.While after blocking β2－AR with ICI118551,the pD2 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 β1－and β2－AR.Rmax mediated by β－AR is reduced but the sensitivity to isoproterenol is increased,which is i[1] [2] [3] 下一页
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