肿瘤坏死因子α介导大鼠心肌梗死后心功能变化的机制
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Mechanisms of Heart Function Change Mediated by Tumor Necrosis Factor-α in the Postmyocardial Infarction Rats
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    摘要:

    为探讨大鼠心肌梗死后衰竭心肌肿瘤坏死因子α表达、基质金属蛋白酶活性和核因子κB活化与心肌胶原含量、心功能的相互关系,通过结扎大鼠冠状动脉前降支复制心肌梗死模型,同时设假手术组,分别在4周、8周和12周后检测血流动力学和心功能指标。同时检测左心室非梗死区心肌肿瘤坏死因子α蛋白水平、核因子κB活性、明胶分解活性和心肌胶原容积指数。结果发现,心肌梗死后心肌肿瘤坏死因子α表达显著增加,呈时间依赖性,与心功能呈负相关;心肌梗死后4周、8周和12周时心肌核因子κB活性、基质金属蛋白酶2和9活性以及胶原容积指数均呈进行性增加,而心功能逐渐恶化。以上说明,衰竭心肌核因子κB持续活化、肿瘤坏死因子α过度表达和明胶分解活性增强可能是导致心肌梗死后心室重塑和心力衰竭的重要机制之一。

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    Aim To investigate the relationship of tumor necrosis factor-α(TNF-α),matrix metalloproteinases(MMPs) and NF-κB on postmyocardial infarction progressive heart failure in rats. Methods Male rats were randomised to proximal left anterior descending branch coronary artery ligation. The rats were killed on weeks 4, 8, and 12 after ligation to examine hemodynamic parameters. Protein expression of TNF-α, MMPs gelatinlytic activity and NF-κB activity was assessed from noninfarcted myocardium, sham-operated rats were used as the control group. Results Compared with sham-operated group, the myocardial infarction rats showed significant decrease in mean arterial pressure(MAP), maximal ascending and descending velocity of the left ventricular pressure(±dp/d tmax) and significant increased in left ventricular end-diastolic pressure(LVEDP) (all p<0.05). In comparison with sham-operated group, TNF-α production was increased significantly, MMP-2 and MMP-9 zymographic activity, NF-κB activity, and collagen volume fraction(CVF) increased significantly at weeks 4, 8 and 12 after ligation in noninfarcted myocardium. Conclusions TNF-α overexpression is related to increase in MMP gelatinlytic activity and NF-κB activity, which suggests that TNF-α can play an important role in postinfarction ventricular remodeling and progressive heart failure.

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谢萍,徐义先,祝善俊,杨铮,高志凌.肿瘤坏死因子α介导大鼠心肌梗死后心功能变化的机制[J].中国动脉硬化杂志,2004,12(6):662~664.

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  • 收稿日期:2004-06-09
  • 最后修改日期:2004-09-30
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