卡维地洛对心肌梗死后心力衰竭大鼠的心肌保护和抗心肌纤维化作用及其机制

Protective effects of carvedilol on myocardium and effect against myocardial fibrosis in rats with heart failure after myocardial infarction

目的:观察卡维地洛对心肌梗死后心力衰竭大鼠心肌纤维化的影响,探讨卡维地洛心肌保护作用机制。方法:Wistar大鼠麻醉后结扎左冠状动脉前降支,术后6周成功建立心力衰竭模型。将32只心力衰竭大鼠随机分为假手术组(n=8)、模型组(n=8)、模型+小剂量卡维地洛组(n=8)和模型+大剂量卡维地洛组(n=8),模型+小剂量卡维地洛组大鼠给予1mg·kg-1·d-1卡维地洛,模型+大剂量卡维地洛组大鼠给予10mg·kg-1·d-1卡维地洛,假手术组和模型组大鼠给予0.5%羧甲基纤维素钠(CMC-Na)10mL·kg-1·d-1,连续给药5周,每日1次。采用硫代巴比妥酸法测定血清中丙二醛(MDA)浓度,采用黄嘌呤氧化酶法测定总血清中超氧化物歧化酶(SOD)活性,采用ELISA法测定血清中脑钠肽(BNP)水平,光镜观察Masson染色下各组大鼠心肌纤维化程度。结果:与假手术组比较,其他3组大鼠血清BNP水平、MDA浓度升高(P<0.05),SOD活性降低;与模型组比较,模型+小剂量卡维地洛组和模型+大剂量卡维地洛组大鼠血清中BNP水平明显降低(P<0.01),血清中MDA浓度显著降低(P<0.01),SOD活性显著升高(P<0.01),且心肌纤维化程度减轻;与模型+小剂量卡维地洛组比较,模型+大剂量卡维地洛组大鼠血清BNP水平降低(P<0.05),MDA浓度降低(P<0.05),SOD活性升高(P<0.05),心肌纤维化程度减轻。结论:不同剂量卡维地洛均有保护心肌、减轻心肌纤维化程度的作用,其机制可能与减少心肌梗死后心力衰竭大鼠血清中MDA浓度、增加SOD活性有关。

Objective To observe the influence of carvedilol in myocardial fibrosis in rats with heart failure after myocardial infarction and to explore the mechanism of protective effect of earvedilol. Methods The left anterior descending coronary arteries of Wistar rats were ligated to establish rat models of heart failure. 32 rat heart failure models were established successfully after 6 weeks. 32 rats with heart failure were divided into sham operation group （n= 8）, model group （n= 8）, model＋low dose of carvedilol group （n= 8）, and model＋ high dose of carvediol group （n=8）. The rats in model＋low or high doses of carvedilol groups were treated with carvediol in low or high doses （1 and 10 mg·kg-1 carvediol） for 7 weeks after the operation. The rats in sham operation and model groups were treated with 0.5·CMC-Na 10 mL·kg-1· d-1. All treatment regimens were initiated 6 weeks after operation and continued for 5 weeks. The activity of serum superoxide dismutase （SOD） was detected by xanthine oxidase method and the concentration of serum malondialdehyde （MDA） was detected by thiobarbituric acid method; the level of serum BNP was detected by ELISA method; after Masson staining, the myocardial fibrosis of these rats were observed under light microscope. Results Compared with sham operation group, the serum BNP level and MDA concentration were increased （P〈0.05） and the activity of SOD was decreased of the rats in the other groups; compared with model group, the concentrations of serum MDA were decreased and the activities of SOD were increased significantly of the in rats in model ＋low or high doses of carvedilol groups （P〈0.01）; the degree of myocardial fibrosis was reduced. Compared with model ＋ low dose of carvedilol group, the serum BNP level was decreased （P〈0.05）, the concentration of MDA was decreased （P〈0.05）, and the SOD activity was increased （P〈0. 05） of the rats in model ＋ high dose of carvedilol group; the degree of myocardial fibrosis was reduced. Conclusion Different doses of earvedilol can protect the myocardium tissue and reduce the degree of myocardial infarction; its mechanism may be related to decreasing the concentration of serum MDA and increasing the activity of serum SOD of the rats with heart failure.