卡维地洛对心梗大鼠远期心室重构的影响及其作用机制

The effect and mechanism of carvedilol long-time ventricular remodeling in rats with myocardial infarction

目的:探讨卡维地洛(Carv)对心肌梗死(MI)大鼠心室心肌重构的影响及其作用机制。方法:结扎30只大鼠左冠状动脉建立MI模型后,随机分为Carv组(n=15)及MI组(n=15)。再另设假手术(Sham)组(n=15)。Carv组给予Carv(日剂量2 mg/kg),分2次灌胃;Sham组及MI组均给予等量蒸馏水灌胃。24周后,观察心室重构和左室非梗死区心肌内4-羟基壬烯醛(4-HNE)和过氧化物丙二醛(MDA)的含量及表达。结果:24周后,超声显示,与Sham组比较,MI组大鼠心功能明显降低,左室舒张末期内径(LVEDD)明显增大,左室短轴缩短率(FS)和心脏射血分数(EF)明显降低(P<0.05,P<0.01)。MI组大鼠左室非梗死区心肌内4-HNE和MDA的含量明显增加,表达明显增强(P<0.05,P<0.01)。Carv组大鼠左室非梗死区心肌组内4-HNE和MDA的含量比MI组明显降低(P<0.05,P<0.01)。结论:MI 6月后,心肌内4-HNE、MDA的活性仍然较高,氧化应激反应仍持续,Carv可以促进活性醛的代谢,对心脏具有保护作用,可改善预后。

AIM： To explore the effect and protective mechanism of carvedilol in long-time ventricular remodeling in rats with myocardial infarction （MI）. METHODS： Rat models with MI were established by the ligation of left anterior descending coronary artery. Rats with myocardial infarction were randomly divided into carvedilol group （Carv, 15 ）, myocardial infarction group （MI, 15 ） and sham-operated group （Sham, 15）. Animals in carvedilol group were treated with carvedilol [2 mg/（kg ·day） ] by gastric gavage and animals in the other two groups were given the same amount of distilled water. After 24 weeks of treatment, the extent of ventricular remodeling and the expression of 4-HNE and MDA were measured in the noninfarcted myocardium. RESULTS： Twenty-four weeks after MI, LVEDD in the MI group significant increased compared with that in the sham group （P 〈 0.05 ）. EF and FS values significant decreased compared with those in the Sham group and the Carv group （P 〈 0. 01 ）. Expression of 4-HNE and MDA in the MI group significantly increased （P 〈 0. 05, P 〈 0. 01 ）. Expression of 4-HNE and MDA in the Carv group decreased compared with that in the MI group （P 〈 0.05, P 〈 0.01 ）. CONCLUSION： Six months after myocardial infarction, the expression of 4-HNE and MDA in noninfarcted myocardium is still active and the oxidative stress reaction is still sustained. Carvedilol can promote the metabolism of active aldehyde, protect the heart and improve the prognosis after MI.