卡维地洛对大鼠心肌梗死后心功能和交感神经重构的影响

Effect of carvedilol on cardiac function and sympathetic nerve remodeling after myocardial infarction in rats

目的探讨卡维地洛(carvedilol)对大鼠心肌梗死(MI)后心功能和心脏交感神经重构的影响。方法 80只雄性Wistar大鼠随机分为MI组(30只)、carvedilol组(30只)和假手术(SO)组(20只),前两组采用结扎左冠状动脉前降支的方法制备MI模型,SO组只开胸,不结扎血管。术后carvedilol组给予每天两次carvedilol5.0mg/kg灌胃处理,MI组和SO组以等量生理盐水灌胃。8周后,采用多道电生理记录仪测定三组大鼠的心率(HR)、左室舒张末压(LVEDP)、左室收缩压(LVSP)和左室压力上升和下降的最大速率(±dp/dt),并用蛋白印记分析和逆转录多聚酶链反应(RT-PCR)分别观察MI后梗死周边区生长相关蛋白43(GAP43)及酪氨酸羟化酶(TH)蛋白含量和mR-NA表达的变化。结果 8周后,与MI组比较,carvedilol组HR和LVEDP显著下降,LVSP和±dp/dt明显上升(P均<0.05);carvedilol组GAP43和TH的蛋白含量与mRNA表达亦明显降低(P<0.05)。结论 carvedilol能显著改善大鼠MI后心功能,并抑制梗死周围区交感神经重构。

Objective To explore the effects of carvedilol on heart function and cardiac sympathetic nerve remodeling after myocardial infarction（MI） in rats. Methods Eighty male Wistar rats were randomly assigned into three groups： MI group （n = 30 ）, carvedilol group（ n = 30 ） and sham operation （SO） group（ n = 20 ）. The model of MI was made by ligation of the left anterior descending artery. The carvedilol group were treated with carvedilol 5 mg/kg twice a day after the operation while the MI group and SO group were treated with saline. Eight weeks later, the heart rate（ HR）, left ventricular end-diastolic pressure（LVEDP）, left ventricular systolic pressure（LVSP） and the maximum rise and fall rate of left ventricular pressure （ -＋ dp/dt） were measured by catheter examination and the expression of growth associated protein 43 （GAP43） and tyrosinehydroxylase （TH） at the peri-infarct zone were examined by western blot and RT-PCR analysis. Results Eight weeks after the operation, both HR and LVEDP in the carvedilol group were markedly decreased （P 〈 0. 05 ）, whereas the LVSP and ± dp/dt were significantly increased （P 〈 0.05 ） compared with the MI group. Furthermore, carvedilol reduced both GAP43 and TH protein production significantly and decreased GAP43 and TH mRNA expression after MI （P 〈 0.05 ）. Conclusions carvedilol may ameliorate cardiac function and inhibit sympathetic nerve sprouting at the peri-infarct zone after MI in rats.