摘要
目的 :探讨核因子 κB (NF κB)活化与充血性心力衰竭大鼠心肌细胞凋亡的关系及卡维地洛(CAR)的作用机制。方法 :观察雄性Waistar大鼠心肌梗死 (MI) 8周后的心肌细胞凋亡指数、心肌总抗氧化能力、丙二醛的浓度、Fas和FasL的mRNA水平、κB抑制蛋白 α (IκB α)表达及NF κB的核结合活性的改变 ,并于MI后 1周对大鼠进行 7周的CAR和美托洛尔 (MET)干预 ,观察CAR和MET对上述指标的影响。结果 :MI后心肌细胞凋亡指数、丙二醛水平、Fas和FasL的mRNA水平、NF κB活性增高 ,IκB α表达下调、总抗氧化能力下降 (P <0 0 5 )。CAR和MET可不同程度地改善心功能指标 (P <0 0 5 ) ,CAR降低心肌细胞凋亡指数、丙二醛浓度、Fas和FasL表达及升高总抗氧化能力的效果优于MET ,并上调IκB α表达、显著降低NF κB活性 (P <0 0 5 )。结论 :氧化应激可激活NF κB ,启动Fas和FasL转录 ,介导心肌细胞凋亡 ,促进MI后充血性心力衰竭的发生、发展。CAR具有抗氧化作用 ,可通过抑制IκB α降解、降低心肌NF κB活性 。
Objective To study the relationship of activation of nuclear factor-κB （NF-κB）and cardiomyocyte apoptosis, the mechanisms of carvedilol （CAR）in therapies for congestive heart failure in rats. Methods Using a animal model of myocardial infarction （MI）, induced by the left coronary artery ligation in male waistar rats, hemodyanmics, ventricular remodeling parameters, the index of cardiac myocyte apoptosis, the concentration of total antioxidation capacity （TAOC）and malondialdehyde （MDA）in myocardium, mRNA levels of Fas and FasL, expression of inhibitoryκB protein-α （κB-α）, and the nuclear DNA binding activity of NF-κB were investigated in the untreated experimental group （MI group）at 8-week after operation and treated experimental groups in which rats were treated with CAR and metoprolol （MET）for 7 weeks since 1 week after operation. Results In the MI group, there were drops in mean arterial pressure, ± dp/dtmax, the expression of IκB-α, and the level of TAOC, and increases in left ventficular end-diastolic pressure, apoptosis index, expression of Fas and FasL mRNA, activity of NF-κB and the concentration of MDA. Both of CAR and MET can improved heart function in rats with MI. The apoptosis index, the concentration of MDA, expression of Fas and FasL mRNA, and activity of NF-κB were significantly lower, the myocardial levels of TAOC and IκB-α was markedly higher in CAR group than those in MET group. Conclusions NF-κB activated by oxidative stress in cardiomyocyte, initiates Fas and FasL gene transcription and induces cardiac myocyte apoptosis and promotes the initiation and progression of congestive heart failure after MI. With antioxidative feature, CAR can effectively decrease myocardiocyte apoptosis by inhibiting degradation of IκB-α and activation of NF-κB.
出处
《中国分子心脏病学杂志》
CAS
2004年第2期67-71,共5页
Molecular Cardiology of China
基金
贵州省科学技术基金资助项目 (No 30 4 4 )
