β3肾上腺素能受体阻断剂对扩张型心肌病大鼠心功能的影响

Effect of β3-adrenoceptor antagonist on cardiac function in dilated cardiomyopathy rats

目的 研究选择性β3肾上腺素能受体（β3-AR）阻断剂SR59230A对扩张型心肌病大鼠心功能的影响。方法 雄性Wistar大鼠72只，随机取14只分为对照组（Nor-C）和用药组（Nor-T），每组7只。其余大鼠应用异丙基肾上腺素制备心力衰竭（简称心衰）模型后，存活大鼠随机分为心衰组（HF-C．8只）和心衰用药组（HF-T，9只）。Nor-T组与HF-T组给予2 mmol／L的SR59230A 0.3ml尾静脉注射．Nor-C组与HF-C组给予同等剂量生理盐水。血流动力学指标测定后，留取左心室心肌组织，测定内皮源性一氧化氮合酶（eNOS）mRNA、β3-AR蛋白表达以及cGMP水平。结果 Nor-T组与Nor-C组比较，大鼠左心室压力最大上升速率（dp／dtmax）及左心室压力最大下降速率（dp／dtmax）绝对值显著增高（P〈0．05）；左心室收缩末期压力（PES）有上升趋势，左心室舒张末期压力（PED）有下降趋势，但差异无统计学意义（P〉0.05）；左心室等容舒张时间常数（Tc）显著缩短（P〈0.05）。HF-T组较HF-C组dp／dtmax、dp／dtmin绝对值及PES著升高（P〈0.05或〈0．01）；而PED、Tc则明显减低（P〈0．05）。HF—C组与Nor—C组比较，eNOS mRNA及β3-AR蛋白表达显著增加（P〈0．01）；而Nor-T组与Nor-C组、HF-T组与HF_C组间差异无统计学意义（P〉0．05）。HF-C组较Nor-C组心肌eGMP水平显著增加（P〈0．01）；Nor-T组与HF-T组cGMP水平分别低于Nor-C组与HF—C组（P〈0．05或〈0.01）。结论 ①β3-AR阻断剂SR59230A可以改善大鼠心功能，尤其以心衰大鼠为著；②心衰时β3-AR、cNOS表达增加，心肌cGMP水平增高；③β3-AR阻断剂改善心功能的作用机制主要是通过抑制cGMP水平实现的。

Objective In order to investigate the effect of a selective β3-adrenoceptor（β3-AR） antagonist SR59230A on cardiac function in dilated cardiomyopathy rats with heart failure. Me,otis 14 rats were randomly chosen from 72 male Wistar rats and equally divided into two groups： normal control group （Nor-C）, normal treatment group （Nor-T）. After a dilated cardiomyopathy model with heart failure being prepared, the survived rats were randomly divided into two groups： 8 in heart failure control group（HF-C）, 9 in heart failure treatment group （HF-T）. Nor-T and HF-T were given SR59230A 0.3 ml（2 mmol/L） via tail-vein, while Nor-C and HF-C were given the equal volume of saline. After hemodynamics was measured, the left ventricles of rats were harvested. Then the expression level of endothelial nitric oxide synthase （CNOS） mRNA, β3-AR protein cGMP level were measured. Results dp/dtmax and absolute value of dp/dtmax in Nor-T were markedly increased（P 〈 0.05） and time constant of left ventricular relaxation （Tc） was markedly shortened（P 〈 0.05） compared with that of Nor-C. Left ventricular endsystolic pressure（PES） had an increase trend while left ventricular end-diastolic pressure（PED） had a decrease trend, however without statistical significance （P 〉 0.05）. dp/dtmax, absolute value of dp/dtmab and PES in HF-T were significantly increased（P 〈 0.05 or 〈 0.01 ）, while PEX and Tc were decreased （P 〈 0.05） compared with those in HF-C. Compared with Nor-C, the expression level of eNOS mRNA and β3-AR protein in HF-C were significantly higher（P 〈 0.01 ）. There were no significant difference between Nor-T and Nor-C or HF-T and HF-C（P 〉 0.05）. The level of cGMP in heart in HF-C was significantly higher than that of Nor-C （P 〈 0.01 ）, significantly lower in Nor-T and HF-T than in Nor-C and HF-C respectively（P 〈 0.05 or 〈 0.01）. Conclusions ①）β3-AR antagonist SR59230A can improve rat cardiac function, especially in heart failure rats. ② The expressions of β3-AR and eNOS increase and the level of cGMP is high in heart failure rats. ③β3-AR antagonist improves cardiac function via inhibiting cGMP.