高级检索

    黄芪百合颗粒调控Keap1/Nrf2信号通路改善高原低氧大鼠肾损伤的机制研究

    Mechanism of Huangqi Baihe Granules Regulating Keap1/Nrf2 Signaling Pathway to Ameliorate Kidney Injury in Hypobaric Hypoxia Rats

      摘要
    • 摘要:
      目的 探讨黄芪百合颗粒对高原低氧模型大鼠肾功能的影响，并基于Keap1/Nrf2信号通路探究其可能的作用机制。
      方法 采用低压低氧舱模拟海拔6000 m，连续暴露7 d，以建立高原低氧大鼠模型。大鼠适应饲养7 d后，黄芪百合颗粒各药物组连续给药14 d，阳性药物组采用腹腔注射给药，并于进舱前连续给药3 d。除空白组外，第15 d起，各组大鼠在实验动物低压模拟舱中模拟海拔6000 m进行低氧暴露，连续7 d。造模结束后处死大鼠，计算大鼠肾脏湿干比与肾指数；采用HE染色法观察各组大鼠肾组织病理形态的变化；使用全自动生化分析仪检测血清中BUN、Cr、UA的含量；试剂盒检测肾组织中SOD活性和GSH、MDA含量；Western blotting和qRT-PCR法检测肾组织中Keap1、Nrf2、HO-1、NQO1蛋白及mRNA表达水平。
      结果 黄芪百合颗粒能够降低高原低氧大鼠肾指数与肾脏湿干重比(P<0.05或P<0.01)，提升高原低氧大鼠SOD活性和GSH含量(P<0.05或P<0.01)，同时降低MDA 水平(P<0.05或P<0.01)；该颗粒还可降低血清中Cr、BUN、UA的含量；提升Nrf2、HO-1、NQO1在大鼠肾组织内的表达(P<0.05或P<0.01)，并减轻大鼠肾组织出血及细胞水肿现象。
      结论 通过现代分子生物学技术揭示了黄芪百合颗粒防治高原低氧大鼠肾损伤的潜在靶点和作用机制，其通过调节 Keap1/Nrf2信号通路来防治高原低氧肾损伤。这为黄芪百合颗粒的后续深入研究提供了方向和思路。

       

      Abstract:
      OBJECTIVE To explore the effects of Huangqi Baihe granules on renal function in plateau hypoxia model rats, and to investigate its possible mechanism of action based on Keap1/Nrf2 signaling pathway.
      METHODS A low-pressure hypoxia chamber was used to simulate an altitude of 6000 m for 7 consecutive days to establish the plateau hypoxia rat model. After 7 days of acclimatization feeding, rats in each Huangqi Baihe granules group were administered the drug continuously for 14 d, while the positive drug group received intraperitoneal injections, with administration for 3 consecutive days prior to entering the chamber. Except for the blank group, rats in all other groups were exposed to simulated hypoxia at 6000 m in the animal low-pressure chamber starting from day 15 for 7 consecutive days. After modeling, the rats were executed to calculate the renal wet-dry ratio and renal index. HE staining was used to observe pathological morphological changes in renal tissues across groups. BUN, Cr and UA levels in serum were detected by fully automated biochemical analyzer. SOD activity and GSH and MDA levels in renal tissues were detected using assay kits. Western blotting and qRT-PCR were employed to detect the protein and mRNA expression levels of Keap1, Nrf2, HO-1, NQO1 in renal tissues.
      RESULTS Huangqi Baihe granules reduced the renal index and wet-dry ratio in plateau hypoxia rats(P<0.05 or P<0.01), elevated SOD activity and GSH content(P<0.05 or P<0.01), and reduced MDA level(P<0.05 or P<0.01). The granules also reduced the content of Cr, BUN and UA in serum, enhance the expression of Nrf2, HO-1 and NQO1 in rat kidney tissues(P<0.05 or P<0.01); and alleviate the phenomena of hemorrhage and cellular edema in rat kidney tissues.
      CONCLUSION The potential target and mechanism of action of Huangqi Baihe granules in preventing and treating renal injury in rats subjected to plateau hypoxia are revealed by modern molecular biology techniques, and the Keap1/Nrf2 signaling pathway can be regulated to prevent and treat renal injury in rats subjected to plateau hypoxia. This provides a direction and insights for further research on Huangqi Baihe granules.

       

      • HTML全文
      • 参考文献(26)
      • 相关文章
      • 施引文献
    • 资源附件(0)

    /

    返回文章
    返回