比索洛尔对慢性心力衰竭大鼠心肌细胞凋亡及心功能的保护作用

目的研究比索洛尔(Biso)对腹主动脉结扎所致慢性心力衰竭大鼠心肌细胞凋亡和心功能的保护作用。方法 SD大鼠40只,随机分为4组,即腹主动脉缩窄(COA)+Vehicle组;COA+Biso组;假手术(Sham)+Vehicle组;Sham+Biso组。Biso干预8周后采用超声心动图和心室插管法评估各组大鼠的心功能,计算左、右心室质量指数(LVMI、RVMI),高敏酶联免疫吸附试验(ELISA)检测血浆去甲肾上腺素(NE)水平,放射免疫法(RIA)检测血浆血管紧张素Ⅱ,AngⅡ水平。用琼脂糖凝胶电泳和TUNEL法观察心肌细胞的凋亡状态,通过反转录聚合酶链反应(RT-PCR)检测凋亡相关基因的表达变化。结果与COA+Vehicle组相比,COA+Biso组大鼠心功能明显改善[LVEF:COA+Biso组:(67±8)%比COA+Vehicle组:(43±8)%,P<0.05],血浆NE[COA+Biso:(570±41)pg/ml比COA+Vehicle:(908±75)pg/ml,P<0.05]和AngⅡ[COA+Biso:(357±49)pg/ml比COA+Vehicle:(476±51)pg/ml,P<0.05]水平降低,未出现细胞凋亡特有的"DNAladder"现象,TUNEL检测凋亡指数减少[COA+Biso:(9.6±0.5)%比COA+Vehicle:(7.2±0.6)%,P<0.05],RT-PCR检测Bax/Bcl-2比例降低[COA+Biso:(114±9)%比COA+Vehi-cle:(137±9)%,P<0.05]。与Sham+Vehicle组相比,COA+Vehicle组大鼠各项心功能指标明显恶化,心肌细胞凋亡较为严重。结论 Biso可降低血浆NE和AngⅡ水平,并通过阻断NE与β1肾上腺素能受体(β1-AR)结合,抑制凋亡相关通路,从而抑制慢性心力衰竭大鼠心肌细胞凋亡,改善心功能,延缓心力衰竭进展。

Protection of Bisoprolol on cardiomyocyte apoptosis and cardiac function in chronic heart failure rats

Objective To investigate the protective effects of Bisoprolol（Biso） on cardiomyocyte apoptosis and- cardiac function in chronic heart failure rats induced by aoaic banded. Methods Forty Sprague-Dawley（SD） rats were randomly divided into 4 groups, coarctation of abdominal aorta（COA±Vehicle）, COA±Biso, sham-operated（Sham±Vehi- cle）, and Sham±Biso. After 8 weeks intervening by Biso, the changes of cardiac function in all groups were evaluated by ultrasound cardiograph and catheterization. Left and fight ventficular mass index was calculated, and plasma nore- pinephfine（NE） and angiotension（AngII） were measured by ELISA and RIA. State of cardiomyocyte apoptosis was observed by agarose gel electrophoresis and TUNEL＇s method and changes of expression in relative apoptosis genes were determined by RT-PCR. Results Compared with COA＋Vehicle group, cardiac function of COA＋Biso group significantly improved [LVEF：COA＋Biso：（67±8）% vs COA＋Vehicle：（43±8）%, P〈0.05],and decreased plasma NE[COA＋Biso： （570±41）pg/ml vs COA：（908±75）pg/ml, P〈0.05] and Ang Ⅱ [COA＋Biso： （356± 49） pg/ml vs COA：（476±51）pg/ml, P〈 0.05]. Moreover, bisoprolol decreased the apoptosis index[COA＋Biso： （9.6±0.5）% vs COA＋Vehicle：（7.2±0.6）%, P〈0.05] and proportion of Bax/Bcl-2 determined by RT-PCR[COA±Biso：（114±9）% vs COA±Vehicle：（137±9）%, P〈0.05], and had no obviously ＂DNA ladder＂ which is particular to apoptosis. Compared with Sham±Vehicle group, each index of cardiac function distinctly aggravated with severe cardiomyocyte apoptosis in COA＋Vehicle. Conclusion Biso could improve cardiac function and inhibit cardiomyocyte apoptosis by decreasing NE and Ang Ⅱ in plasma and blocking β1-adrenergic receptor in aortic banded rats.