卡维地洛对慢性心力衰竭β_3肾上腺素能受体表达的影响

Effect of carvedilol on β_3-adrenoceptor expression in chronic heart failure

目的:探讨慢性心力衰竭大鼠β3肾上腺素能受体(β3受体)表达以及不同剂量的卡维地洛对其的干预效果。方法:32只雄性Wistar大鼠分为假手术组(n=10)和心力衰竭组(n=22)。心力衰竭组大鼠分别予生理盐水(心力衰竭对照组,n=6)、低剂量卡维地洛(3mg·kg-1.d-1,n=8)或高剂量卡维地洛(6mg·kg-1.d-1,n=8)口服灌注,共3个月。结果:与假手术组比较,心力衰竭组大鼠左室收缩末压、左室内压最大收缩和舒张速率的绝对值显著降低(P<0.01),左室舒张末压显著增高(P<0.01)。与低剂量卡维地洛组比较,高剂量卡维地洛组LVESP及dp/dtmax明显升高、LVEDP明显降低(P<0.01)。高剂量卡维地洛组的左心室质量指数明显低于低剂量卡维地洛组和心力衰竭对照组(P<0.01)。研究组左心室β3受体表达明显高于假手术组(P<0.01)。高剂量卡维地洛组大鼠左心室β3受体表达明显低于假手术组和低剂量卡维地洛组(P<0.01)。结论:大鼠衰竭左心室的β3受体表达明显增加。高剂量卡维地洛对大鼠心力衰竭后血流动力学、左心室重构的改善作用明显优于低剂量时。高剂量卡维地洛明显抑制大鼠衰竭左心室β3受体表达,而低剂量卡维地洛没有此作用。

OBJECTIVE To investigate the expression of β3-adrenoceptor in rats with chronic heart failure, and to explore the effect of carvedilol on β3-adrenoceptor expression. METItODS Thirty-two male Wistar rats were divided into sham （n = 10） and heart failure （n = 24） groups. Heart failure group was treated with normal saline （heart failure control, n = 6）, low dose carvedilol（3 mg·kg^-1·d^-1, n = 8） or high dose carvedilol（6 mg·kg^-1·d^-1, n = 8） for three months. RESULTS The left ventricular end systolic pressure（LVESP） and the absolute values of maximal rate of rise and fall of left ventricular pressure（dp/dtmax） in the heart failure group were lower than in the Sham group （P〈0. 01）, whereas the left ventricular end diastolic pressure（LVEDP） was higher （P〈0. 01）. The LVESP and dp/dtmax in the high dose carvedilol group were higher than low dose carvedilol group whereas LVEDP was lower （P〈0. 01）. The left ventricular mass index（LVMI） in high dose carvedilol group was less than the low dose carvedilol and the heart failure control groups（P〈0. 01）. The level of β3-adrenoceptor expression in left ventricle in the study groups was significantly higher than the sham group（P〈0. 01）. β3-adrenoceptor expression in the high dose carvedilol group, was lower than the heart failure control group and the low dose carvedilol group（P〈0. 01）. CONCLUSION β3-adrenoceptor expression is increased in the failing left ventricle in rats. High dose carvedilol is more effective than low dose in improving hemodynamics and in attenuating left ventricular remodeling after heart failure. High dose carvedilol, rather than low dose, diminishes β3-adrenoceptor expression in the failing left ventricle.