美托洛尔对心力衰竭大鼠心脏β_3肾上腺素能受体mRNA表达水平的影响

Effect of Metoprolol on β_3-adrenoceptor mRNA Expression in Rats with Chronic Heart Failure

【目的】探讨心力衰竭大鼠心脏β3肾上腺素能受体(β3受体)mRNA表达,以及β受体阻滞剂美托洛尔对其的干预效果。【方法】28只大鼠随机分为假手术组(n=10)和心力衰竭组(n=18),主动脉缩窄法建立心衰模型。3个月后心力衰竭组存活16只分为心衰对照组,美托洛尔组,每组8只。美托洛尔组以美托洛尔6mg·kg-·1d-1口服灌注,心衰对照组灌注等量生理盐水。口服灌注3个月后检测血流动力学,心室质量指数及RT鄄PCR方法测定心室β3受体mRNA表达。【结果】与假手术组比较,心衰对照组大鼠心率明显增快(P<0.05),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,左室舒张末压显著增高(P均<0.01)。美托洛尔组大鼠血流动力学参数明显改善(P<0.01)。与假手术组比较,心衰对照组大鼠心室质量指数明显增加,美托洛尔组大鼠较心衰对照组明显下降(P<0.01)。心衰对照组、美托洛尔组心室β3受体mRNA表达明显高于假手术组(P<0.01),但心衰对照组、美托洛尔组之间比较无统计学意义(P>0.05)。【结论】心衰大鼠心脏β3受体mRNA表达明显增加。美托洛尔可以改善心衰大鼠的血流动力学,明显抑制心室重塑,但对心室β3ARmRNA表达无显著影响。

Objective]To investigate the changes of β3-adrenoceptor (β3AR) mRNA expression in the rats with heart failure, and to explore the effect of metoprolol on β3 mRNA expression. [Methods] Twenty-eight rats were randomly divided into sham operated group (n=10) and heart failure group (n=18). Rat model was established by aortic constriction. The rats in heart failure group were divided into heart failure control group and metoprolol group three months after operation (eight rats in each group). Metoprolol was started orally with 6 mg·kg-1·d-1, isometric saline was started in heart failure control group. After three months of drug therapy, measurement of hemodynamics, index of ventricular weight, the level of βAR mRNA expression were performed. [Results] Compared with sham operated group, left ventricular end systolic pressure (LVESP), and the absolute values of maximal rate of rise and fall (±dp/dt) of left ventricular pressure were all significantly decreased (P< 0.01), left ventricular end diastolic pressure (LVEDP) was significantly increased in heart failure control group (P< 0.01). In comparison with heart failure control group, the hemodynamic index was significant improved in metoprolol group (P< 0.01). The index of ventricular mass was higher in heart failure control group than metoprolol group and Sham group (P< 0.01). Compared with Sham group, the level of β3AR mRNA expression was significantly increased in heart failure control group and metoprolol group (P< 0.01), but there was no significant difference between the two groups (P >0.05). [Conclusion]The level of β3AR mRNA expression remarkably increased in the rats' ventricles with heart failure. Metoprolol can effectively attenuate left ventricular remodeling and improve hemodynamics, but has no effect on β3AR mRNA expression.