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

关键词:  黄芪百合颗粒  高原低氧  Keap1/Nrf2  氧化应激  肾损伤

Key words:  Huangqi Baihe Granules  hypobaric hypoxia  Keap1/Nrf2  Oxidative stress  Kidney injury

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米连续暴露7d以复制高原低氧大鼠模型，适应饲养7 d后，黄芪百合颗粒各药物组大鼠连续给药14 d,阳性药物组给予腹腔注射，进舱前连续给药3 d。除空白组外，第15 d起各组大鼠于实验动物低压模拟舱中模拟海拔6000米进行低氧暴露，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；HE法观察各组大鼠肾组织病理形态的变化；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 blot和qRT-PCR法检测肾组织中Keap1、Nrf2、HO-1、NQO1蛋白及mRNA表达；结果 黄芪百合颗粒可以减轻高原低氧大鼠肾指数与肾脏湿干重比（P ＜ 0.05，P ＜ 0.01），黄芪百合颗粒可提升高原低氧大鼠SOD活性和GSH含量 （P ＜ 0.05，P ＜ 0.01）、降低MDA 水平（P ＜ 0.05，P ＜ 0.01）；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，P ＜ 0.01）；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；可通过调节 Keap1/Nrf2信号通路来防治高原低氧肾损伤。这为未来对黄芪百合颗粒的更深入研究提供了方向和思路。

Abstract:

ABSTRACT：OBJECTIVE To explore the effects of Astragalus Lilium Granules on renal function in rats modeled with plateau hypoxia, and to investigate its possible mechanism of action based on Keap1/Nrf2 signaling pathway. METHODS A low-pressure hypoxia chamber was used to simulate the exposure to 6000 m above sea level for 7 consecutive days to replicate the plateau hypoxia rat model, and after 3 d of acclimatization, Huangqi Baihe Granules were administered to rats of each drug group for 14 consecutive days, and the positive drug group was given intraperitoneal injections, and was administered for 3 consecutive days prior to the entry into the chamber. At the end of modeling, the rats were executed to calculate the wet-to-dry ratio and renal index of the kidneys; HE method was used to observe the changes of renal histopathology and morphology in each group of rats; 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 by the kit; and Keap1, Nrf2, HO-1, NQO1 were detected by Western blot and qRT-PCR methods in the renal tissues, Nrf2, HO-1, NQO1 protein and mRNA expression in renal tissues; RESULTS Huangqi Baihe Granules could reduce the ratio of renal index to wet-dry weight arm of kidneys in plateau hypoxia rats (P < 0.05, P < 0.01), Huangqi Baihe Granules elevated the SOD activity and GSH content in plateau hypoxia rats (P < 0.05, P < 0.01), reduced the level of MDA (P < 0.05, P < 0.01); reduce 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, 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 were revealed by modern molecular biology techniques, and the Keap1/Nrf2 signaling pathway could be regulated to prevent and treat renal injury in rats subjected to plateau hypoxia. This provides a direction and idea for more in-depth research on Huangqi Baihe Granules in the future.