方典, 梁欢, 王佳慧, 汪敬业, 李正红, 高琴. 线粒体细胞色素c释放抑制剂对大鼠全脑缺血再灌注损伤炎症反应的作用[J]. 蚌埠医科大学学报, 2022, 47(1): 7-12. DOI: 10.13898/j.cnki.issn.1000-2200.2022.01.002
    引用本文: 方典, 梁欢, 王佳慧, 汪敬业, 李正红, 高琴. 线粒体细胞色素c释放抑制剂对大鼠全脑缺血再灌注损伤炎症反应的作用[J]. 蚌埠医科大学学报, 2022, 47(1): 7-12. DOI: 10.13898/j.cnki.issn.1000-2200.2022.01.002
    FANG Dian, LIANG Huan, WANG Jia-hui, WANG Jing-ye, LI Zheng-hong, GAO Qin. Effect of mitochondrial cytochrome c release inhibitor on the inflammatory response of rats with global cerebral ischemia reperfusion injury[J]. Journal of Bengbu Medical University, 2022, 47(1): 7-12. DOI: 10.13898/j.cnki.issn.1000-2200.2022.01.002
    Citation: FANG Dian, LIANG Huan, WANG Jia-hui, WANG Jing-ye, LI Zheng-hong, GAO Qin. Effect of mitochondrial cytochrome c release inhibitor on the inflammatory response of rats with global cerebral ischemia reperfusion injury[J]. Journal of Bengbu Medical University, 2022, 47(1): 7-12. DOI: 10.13898/j.cnki.issn.1000-2200.2022.01.002

    线粒体细胞色素c释放抑制剂对大鼠全脑缺血再灌注损伤炎症反应的作用

    Effect of mitochondrial cytochrome c release inhibitor on the inflammatory response of rats with global cerebral ischemia reperfusion injury

    • 摘要:
      目的探讨线粒体细胞色素c抑制剂对大鼠全脑缺血再灌注后脑损伤的作用,分析线粒体乙醛脱氢酶2(ALDH2)和炎症反应在其中的机制。
      方法通过四血管阻断法模拟大鼠全脑缺血再灌注损伤(I/R)模型,雄性SD大鼠随机分为假手术组(Sham组)、I/R组、ALDH2激动剂Alda-1+I/R组、Bax介导的线粒体细胞色素c释放抑制剂(Bcb)+I/R组。HE染色观察海马CA1区细胞形态学的变化;免疫组织化学观察海马CA1区ALDH2及炎症小体关键蛋白NLRP3表达水平,Western blotting检测海马CA1区4-HNE、NLRP3、IL-1β、IL-18及ALDH2的蛋白水平变化。
      结果与Sham组比较,I/R组再灌注7 d后,I/R组海马CA1区细胞存活率明显下降;与I/R组比较,Alda-1+I/R组、Bcb+I/R组的海马CA1区神经元存活率增高(P < 0.01)。与I/R组相比,Bcb+I/R组、Alda-1+I/R组海马CA1区ALDH2蛋白表达增加,海马CA1区NLRP3、IL-1β、IL-18、4-HNE蛋白表达下降(P < 0.01)。
      结论大鼠全脑缺血再灌注损伤模型中,海马CA1区NLRP3表达增高;Bcb可以通过促进线粒体ALDH2的表达、降低炎症反应发挥保护作用。

       

      Abstract:
      ObjectiveTo explore the effects of mitochondrial cytochrome c inhibitor on the cerebral injury in rats with global cerebral ischemia-reperfusion injury, and analyze the possible mechanisms of mitochondrial aldehyde dehydrogenase 2(ALDH2)and inflammatory response.
      MethodsThe rat model with global cerebral ischemia and reperfusion injury(I/R) was simulated by four-vessel occlusion.The male SD rats were randomly divided into the sham group, I/R group and ALDH2 agonist Alda-1+I/R group and Bax-mediated mitochondrial cytochrome c release inhibitor(Bcb)+I/R group.The HE staining was used to observe the morphological changes of hippocampal CA1 cells.The expressions of ALDH2 protein and inflammasome-related protein NLRP3 in hippocampal CA1 were observed by immunohistochemistry.The protein changes of 4-HNE, NLRP3, IL-1β, IL-18 and ALDH2 in hippocampal CA1 were detected by Western blotting.
      ResultsCompared with the sham group, the survival rate of hippocampal CA1 region cells in the I/R group decreased significantly after 7 d of reperfusion(P < 0.01).Compared with the I/R group, the survival rate of hippocampal CA1 neurons in ALDA-1 +I/R group and Bcb+I/R group increased(P < 0.01).Compared with the I/R group, the expression of ALDH2 protein increased in Bcb+I/R group and ALDA-1 +I/R group, while the expressions of NLRP3, IL-1β, IL-18 and 4-HNE proteins in hippocampal CA1 region decreased(P < 0.01).
      ConclusionsThe expression of NLRP3 in hippocampal CA1 increases in rats with global cerebral I/R injury model.The Bcb may play a protective role by promoting the mitochondrial ALDH2 expression and reducing inflammatory response.

       

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