长期饮用普萘洛尔对大鼠心脏和血淋巴细胞β肾上腺素受体效应及亚型的影响

Effects of long term propranolol treatment on β adrenoceptor response and subtypes in rat hearts and lymphocytes 1

采用放射配体结合实验，离体左心房收缩功能实验，逆转录聚合酶链反应及高效液相色谱等方法研究长期饮用普萘洛尔（７０ｍｇｋｇ－１ｄ－１，８ｗｋ）对大鼠心脏β肾上腺素受体（β－ＡＲ）及其亚型，外周血淋巴细胞β２－ＡＲ和血浆儿茶酚胺水平的影响．结果表明长期饮用普萘洛尔后：（１）心脏β－ＡＲ密度从对照组的４１±８ｐｍｏｌｇ－１蛋白上调到６１±９ｐｍｏｌｇ－１蛋白，ＣＧＰ２０７１２Ａ竞争抑制曲线２位点分析结果显示为β１和β２－ＡＲ同等程度上调；（２）心脏β１－ＡＲｍＲ－ＮＡ水平不变而β２－ＡＲｍＲＮＡ水平显著增加；（３）β－ＡＲ及其亚型介导的离体左心房正性变力效应增强，以β２－ＡＲ的功能改变更为显著；（４）血淋巴细胞β２－ＡＲ数目从对照组的１９±７ｐｍｏｌｇ－１蛋白上调至３２±８ｐｍｏｌｇ－１蛋白；（５）血浆去甲肾上腺素水平（０．２１±０．１２μｇＬ－１）明显低于对照组（０．３８±０．１５μｇＬ－１）．

The effects of long term treatment with nonselective β adrenoceptor(β AR) antagonist propranolol (70 mg·kg 1 ·d 1 , in drinking water for 8 weeks) on β AR subtypes in rat hearts and lymphocytes, and plasma concentration of catecholamine were studied by radioligand binding assay, functional experiment of isolated perfused left atrias, reverse transcription polymerase chain reaction and high performance liquid chromatography methods. The results indicated that after long term propranolol treatment: (1) the density of total β AR in the hearts was up regulated from 41±9 pmol·g 1 protein in control group to 61±9 pmol·g 1 protein, the competitive inhibition curves of CGP20712A for [ 125 I] pindolol showed that the numbers of β 1 and β 2 AR were up regulated to the same extent; (2) β 1 AR mRNA level was not changed, but β 2 AR mRNA level was increased significantly in hearts; (3) the positive inotropic response induced by activation of β AR and subtypes was markedly enhanced, functional alteration was more significant in β 2 AR than that in β 1 AR; (4) the numbers of β 2 AR in lymphocytes were increased from 19±8 pmol·g 1 protein in control group to 32±8 pmol·g 1 protein; (5) plasma concentration of norepinephrine was decreased obviously in propranolol group (0.21±0.12 μg·L 1 ) compared with control group (0.38±0.15 μg·L 1 ).