高血压糖尿病大鼠心脏β肾上腺素能受体及其亚型的改变  

Alteration of Cardiac β-adrenoceptor and Its Subtypes in Hypertensive-diabetic Rats

作　　者：宫海滨[1] 王雷[1] 王洁[1] 张幼怡[2] 

机构地区：[1]江苏省徐州市心血管病研究所,徐州市中心医院,221009 [2]北京大学第三医院血管医学研究所

出　　处：《中国微循环》2009年第2期90-92,110,共4页Journal of Chinese Microcirculation

基　　金：国家自然科学基金资助项目(No.30572073);江苏省自然科学基金资助项目(BK2005428);江苏省"六大人才高峰"第三批资助项目(C类);江苏省医学重点人才(RC2007024)

摘　　要：目的研究高血压糖尿病大鼠心脏β肾上腺素能受体(β-AR)及其亚型的改变。方法采用高血压糖尿病大鼠动物模型,放射配体结合实验和离体左心房收缩功能实验观察高血压糖尿病大鼠心脏β-AR及其亚型的改变。结果高血压糖尿病大鼠心脏β-AR的最大结合容量(Bmax)较对照组增加35%(P<0.01),KD值不变。CGP20712竞争抑制曲线两位点分析显示β1-AR和β2-AR之间比例未发生改变。高血压糖尿病组在异丙肾上腺素(ISO)激动下β-AR介导的最大收缩反应(Rmax)较对照组下降48%(P<0.01),而pD2值不变。CGP20712阻断β1-AR后,β2-AR介导心肌的Rmax不变,而pD2值显著低于对照组(P<0.05);ICI118551阻断β2-AR后,β1-AR介导心肌的Rmax和pD2值均显著低于对照组(P<0.05)。结论高血压糖尿病大鼠心脏β-AR总数明显上调,且β1-AR和β2-AR上调的程度相同;β-AR介导心肌最大收缩反应的降低,主要是由β1-AR的改变引起,β-AR对ISO敏感性不变,而β1-AR和β2-AR则分别发生减敏。Objective To observe the alteration of cardiac β-adrenoceptor（β-AR） and its subtypes in hypertensive-diabetic rats. Methods The changes were studied by radioligand binding assays and functional determination of isolated left atria. Results β-AR density was increased by 35 % （ P 〈 0.01） and the KD value was not changed in hypertensive-diabetic rats. The two-site analysis of CGP20712 competitive inhibition curves indicated that the ratio of two β-AR subtypes was not significantly changed. The maximal positive inotropic response induced by isoproterenol （Rmax） was decreased by 48% （P 〈 0.01）, and the pDz value was not altered in hypertensive-diabetic rats. After blocking β1-AR with CGP20712, the Rmax was not changed, and the pD2 value was significantly decreased in hypertensive-diabetic rats. While after blocking β2-AR with ICI118551, the Rmax and the pDz value were all decreased significantly. Conclusion In hypertensivediabetic rats cardiac β-AR was significantly upregulated, with the same degree for the β1-and β2-AR. The β-AR mediated Rmax was decreased, which was induced by alteration of β1-AR. The sensitivity of β-AR to isoproterenol was unchanged, but the desensitization of β1- and β2-AR occurred, respectively.

关 键 词：高血压 糖尿病 Β肾上腺素能受体 受体亚型 心脏 

分 类 号：R544.1[医药卫生—心血管疾病]