尼可地尔改善心肌细胞缺氧/复氧损伤引起的炎症反应

    Nicorandil improves inflammatory response induced by myocardial cells hypoxia/reoxygenation injury

      摘要
    • 摘要:
      目的 探讨尼可地尔在心肌缺血/再灌注损伤（ischemia/reperfusion injury, I/RI）中的保护作用，为尼可地尔的临床应用开拓新的思路。
      方法 应用细胞进行实验：培养H9C2心肌细胞缺氧处理4 h随即复氧处理12 h，建立心肌细胞缺氧/复氧（hypoxia/reoxygenation, H/R）模型，模拟心肌I/RI。通过Western blot检测细胞中磷酸化核因子κBp65（phosphorylated nuclear factor kappa-B p65，p-NFκBp65）、磷酸化核因子κB抑制蛋白α（phosphorylated inhibitor of nuclear factor kappa-B alpha，p-IκBα）、核因子κBp65（nuclear factor kappa-B p65，NFκBp65）和核因子κB抑制蛋白α（inhibitor of nuclear factor kappa-B alpha，IκBα）的蛋白表达，ELISA检测细胞中炎性因子肿瘤坏死因子（tumor necrosis factor-alpha，TNF-α）、白细胞介素6（interleukin 6，IL-6）及白细胞介素1β（interleukin 1β，IL-1β）的表达，并应用尼可地尔及其抑制剂5-羟基癸酸酯（5-Hydroxydecanoate，5-HD）进行干预，以明确尼可地尔对于I/RI心肌细胞炎症反应的影响。
      结果 与Control组相比，H/R组H9C2细胞TNF-α、IL-6及IL-1β的表达显著上升（P<0.01），p-NFκB p65和p-IκBα的蛋白表达显著上升（P<0.01），NFκBp65和IκBα的蛋白表达没有明显的变化。加入尼可地尔后TNF-α、IL-6及IL-1β的表达显著下降（P<0.01），p-NFκBp65和p-IκBα的蛋白表达显著下降（P<0.01），NFκBp65和IκBα的蛋白表达没有明显变化。与H/R+尼可地尔组相比，加入5-HD后TNF-α、IL-6及IL-1β的表达显著上升（P<0.01），p-NFκBp65和p-IκBα的蛋白表达显著上升（P<0.01），NFκBp65和IκBα的蛋白表达没有明显变化。
      结论 尼可地尔可以改善H/R损伤诱导的心肌细胞炎症反应，该作用可被5-HD逆转。

       

      Abstract:
      AIM To explore the protective effects of nicorandil in myocardial ischemia/reperfusion injury (I/RI) and develop new ideas for the clinical application of nicorandil.
      METHODS H9C2 myocardial cells were incubated in hypoxic conditions for 4 hours and then reoxygenated for 12 hours to create hypoxia/reoxygenation (H/R) paradigm of cardiomyocytes for simulating myocardial I/RI. The expressions of p-NF-κBp65 and p-IκBa were determined by Western blot. ELISA was performed to examine the expressions of intracellular inflammatory factors TNF-α, IL-6 and IL-1β, and nicorandil and its inhibitor 5-Hydroxydecanoate (5-HD) were applied to intervene to clarify the effects of nicorandil on the inflammatory response.
      RESULTS In H9C2 cells, H/R promoted inflammatory response. Compared with those in the control group, in the H/R group the expressions of TNF-α, IL-6 and IL-1β were significantly increased (P<0.01), the protein expressions of p-NFκBp65 and p-IκBa were also significantly increased (P<0.01), and no obvious changes were observed in protein expressions of NFκBp65 and IκBa. Nicorandil alleviated the effects of H/R-induced H9C2 cells. In contrast to those in the H/R group, the expressions of TNF-α, IL-6 and IL-1β were significantly reduced and the protein expressions of p-NFκBp65 and p-IκBa were also significantly reduced (P<0.01) after adding 100 μM nicorandil (P<0.01). The effects that nicorandil affected H/R-induced H9C2 cells could be inhibited by 5-HD. Compared with those in the nicorandil+H/R group, the expressions of TNF-α, IL-6 and IL-1β were significantly higher and the protein expressions of p-NFκBp65 and p-IκBa were significantly increased after adding 250 μM 5-HD (P<0.01). No significant changes in protein expressions of NFκBp65 and IκBa were shown under different treatment conditions.
      CONCLUSIONS Nicorandil ameliorates the H/R-induced inflammatory response in cardiomyocytes, which can be reversed by 5-HD.

       

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