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

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.