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目的:探讨慢性心力衰竭(HF)兔心肌核因子-κB(NF-κB)活化、诱生型一氧化氮合酶(iNOS)与心肌细胞凋亡的关系以及N-乙酰半胱氨酸(NAC)对心肌细胞凋亡的作用。方法:设立对照组,剩余动物以阿霉素复制HF模型,随机分为HF组和NAC组,药物干预4周。观测3组心肌细胞凋亡指数、血清和心肌一氧化氮(NO)浓度、iNOS蛋白在心肌细胞中表达的水平,以及NF-κB p65的核表达和结合活性的改变,观察NAC对上述指标的影响。结果:与对照组比较,HF组心肌细胞凋亡指数增高,iNOS蛋白表达增多,NF-κB p65易位和核内表达增多,血清和心肌NO浓度升高(P<0.001),NF-κB p65活化与iNOS表达呈直线相关(r=0.973,P<0.001)。NAC组结果示NAC可显著减少NF-κB p65核内表达及iNOS蛋白的表达,降低血清和心肌NO水平,降低心肌细胞凋亡指数(P<0.01～0.001)。结论:HF时心肌细胞中NF-κB的活化及其促进iNOS的转录合成导致NO大量生成,参与了心肌凋亡的发生。NAC可显著拮抗NF-κB的大量活化核表达,减弱iNOS的表达上调,抑制NO的生成,减少心肌细胞凋亡。NF-κB的活化可能是iNOS表达的重要调控机制之一。
Objective: To investigate the relationship between the activation of nuclear factor-κB (NF-κB) and the expression of inducible nitric oxide synthase (iNOS) and cardiomyocyte apoptosis in chronic heart failure (HF) ) On cardiomyocyte apoptosis. Methods: The control group was established. The remaining animals were treated with doxorubicin to duplicate HF model and were randomly divided into HF group and NAC group. The drug intervention was for 4 weeks. The apoptotic index, the concentration of serum and myocardial nitric oxide (NO), the expression of iNOS in cardiomyocytes and the nuclear expression and binding activity of NF-κB p65 were observed in 3 groups. The effects of NAC on the above indexes influences. Results: Compared with the control group, the apoptosis index of cardiomyocytes in HF group was increased, the expression of iNOS protein increased, the expression of NF-κB p65 translocation and nucleus increased, the concentration of NO in serum and myocardium increased (P <0.001) There was a linear correlation between activation and iNOS expression (r = 0.973, P <0.001). The results of NAC group showed that NAC can significantly reduce the nuclear expression of NF-κB p65 and the expression of iNOS protein, decrease the level of NO in serum and myocardium, and decrease the apoptosis index of cardiomyocytes (P <0.01 ~ 0.001). Conclusion: The activation of NF-κB in cardiomyocytes and the promotion of iNOS transcriptional synthesis resulted in the massive production of NO, which involved in the occurrence of myocardial apoptosis. NAC can significantly antagonize the activation of NF-κB nuclear expression, weakened the iNOS expression increased, inhibited the generation of NO and decreased cardiomyocyte apoptosis. Activation of NF-κB may be one of the important regulatory mechanisms of iNOS expression.