姜黄素调节NRF2/FPN1信号通路对糖尿病合并冠心病大鼠心肌损伤的影响

    Effects of curcumin on myocardial injury in rats with diabetes and coronary heart disease by regulating NRF2/FPN1 signaling pathway

    • 摘要:
      目的 探讨姜黄素(curcumin,CUR)对糖尿病合并冠心病大鼠心肌损伤及核因子E2相关因子2/膜铁转运蛋白1(NRF2/FPN1)信号通路的影响。
      方法 构建大鼠模型并将其随机分为模型组(Model组)、姜黄素低、中、高剂量组(CUR-L、CUR-M、CUR-H组)、姜黄素高剂量+通路抑制剂ML385组(CUR-H+ML385组),每组12只,另取12只健康大鼠作为对照组(Control组)。对所有大鼠进行血生化指标检测,超声心动图观察心功能指标,HE染色观察心肌组织形态,TUNEL染色观察心肌组织细胞凋亡情况,Western blot检测NRF2/FPN1信号通路有关蛋白表达。
      结果 与Control相比,Model组大鼠心肌组织整体结构破环、病理损伤严重,心肌细胞凋亡率提高,FPG、TG、LPa、D-D、FIB水平和LVEDD、LVESD指标、铁离子含量均显著升高,INS水平、HR、LVEF指标和NRF2、FPN1蛋白表达量明显降低(P<0.05,P<0.01);与Model组相比,随着CUR剂量的增加,CUR-L、CUR-M、CUR-H组心肌组织整体结构逐渐恢复完整、病理损伤减轻,心肌细胞凋亡率减小,FPG、TG、LPa、D-D、FIB水平和LVEDD、LVESD指标、铁离子含量逐渐降低,INS水平、HR、LVEF指标和NRF2、FPN1蛋白表达量逐渐升高(P<0.05,P<0.01);与CUR-H组相比,CUR-H + ML385组大鼠心肌组织整体结构破环、病理损伤较重,心肌细胞凋亡率提高,FPG、TG、LPa、D-D、FIB水平和LVEDD、LVESD指标、铁离子含量均显著升高,INS水平、HR、LVEF指标和NRF2、FPN1蛋白表达量均显著降低(P<0.01)。
      结论 姜黄素可能通过激活NRF2/FPN1信号通路改善糖尿病合并冠心病大鼠心肌组织损伤,增强心保护功能。

       

      Abstract:
      AIM To investigate the effects of curcumin (CUR) on myocardial injury and nuclear factor erythroid 2 related factor 2/ferroportin 1 (NRF2/FPN1) signaling pathway in rats with diabetes and coronary heart disease.
      METHODS A rat model was constructed and randomly separated into model group, low, medium, and high-dose curcumin groups (CUR-L, CUR-M, CUR-H groups), and high-dose curcumin+pathway inhibitor ML385 group (CUR-H+ML385 group), with 12 rats in each group. An additional 12 healthy rats were selected as the control group. All rats were tested for blood biochemical indicators. Echocardiogram was applied to observe cardiac function indicators, HE staining was applied to observe the morphology of myocardial tissue, TUNEL staining was applied to observe the apoptosis of myocardial tissue cells and Western blot was applied to detect protein expression related to the NRF2/FPN1 signaling pathway.
      RESULTS Compared with those in the control group, the overall structure of myocardial tissue in the model group was disrupted, with severe pathological damage, the myocardial cell apoptosis rate increased, FPG, TG, LPa, D-D and FIB levels, LVEDD and LVESD indicators and iron ion content were obviously increased, and INS level, HR and LVEF indicators and NRF2 and FPN1 protein expression levels were obviously reduced (P<0.05, P<0.01). Compared with those in the model group, with the increase of CUR dose, the overall structure of myocardial tissue in the CUR-L, CUR-M and CUR-H groups gradually recovered, pathological damage was reduced and the apoptosis rate of myocardial cells decreased. FPG, TG, LPa, D-D and FIB levels, LVEDD and, LVESD indicators and iron ion content were gradually reduced, and INS level, HR and LVEF indicators and NRF2 and FPN1 protein expression levels were gradually increased (P<0.05, P<0.01). Compared with those in the CUR-H group, the myocardial tissue of rats in the CUR-H+ML385 group showed overall structural rupture and more severe pathological damage, the myocardial cell apoptosis rate increased, FPG, TG, LPa, D-D and FIB levels, LVEDD and LVESD indicators and iron ion content were obviously increased, and INS level, HR and LVEF indicators and NRF2 and FPN1 protein expression levels were obviously reduced (P<0.01).
      CONCLUSION Curcumin improves myocardial tissue damage and enhances cardiac protection function in rats with diabetes and coronary heart disease by activating NRF2/FPN1 signaling pathway.

       

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