Study on the Protective Effect of Astragaloside Ⅳ on Liver Oxidative Stress Injury in Rats Induced by Simulated acute Plateau Exposure based on Nrf2/HO-1 Pathway
Objective:To investigate the effects of hypoxia at different time on the level of liver oxidative stress and the changes in liver and kidney function,and to study the protective effect of astragaloside Ⅳ on the liver of rats simu-lated acute plateau exposure based on the Nrf2/HO-1 pathway. Methods:An animal model of simulated acute plateau hypoxia was established. 56 SD rats were randomly divided into a control group (Control),a hypoxia group (H),and an astragaloside Ⅳ group (AS-Ⅳ+H). The H group and the AS-Ⅳ+H group were further divided into 12 h,24 h,and 48 h subgroups,with 8 rats in each group,for a total of 7 groups. The AS-Ⅳ+H group was given astragaloside Ⅳ by gavage (80 mg/kg),once a day,for 7 consecutive days. The rats in the experimental group were placed in a hypobaric oxygen chamber (simulating an altitude of 5000 m). After the predetermined time,the liver and kidney function of the rats in serum,the content of superoxide dismutase (SOD),malondialdehyde (MDA),and glutathione peroxidase (GSH-PX) in liver tissue were detected respectively;the protein expression and gene expression level of Nrf2 and HO-1 in liver tis-sue were detected by Western blotting and fluorescence quantitative PCR respectively;the pathological manifestations of liver tissue were observed by HE staining. Results:Compared with the control group in normoxic environment,the liver and kidney function indexes of the H group and AS-Ⅳ+H group at different hypoxic time periods were higher than those of the control group,and showed an increasing trend with the increase of hypoxia time (P<0.05,P<0.01). In the tissue homogenate,except for MDA,the levels of other antioxidant enzymes,superoxide SOD and GSH-PX,were lower than those of the control group (P<0.05 or P<0.01). The expression of Nrf2 and HO-1 protein and mRNA in liver tissue increased with the extension of hypoxia time,reaching the peak at 24h hypoxia,and decreased at 48h hypoxia compared with 24h hypoxia,but was higher than that in the control group at all time periods (P<0.05,P<0.01). Compared with the hypoxia group at the same time,the liver and kidney function,SOD,and GSH-PX in the astragaloside Ⅳ group were lower than those in the hypoxia group at the same time,but MDA was higher than those in the hypoxia group at the same time (P<0.05,P<0.01). The expression of Nrf2 and HO-1 protein and mRNA in liver tissue were higher than those in the hypoxia group at the same time (P<0.05,P<0.01). HE staining showed that the hepatocytes in the hypoxia group were edematous,and the edema in the astragaloside Ⅳ group was alleviated. Conclusion:Rapid exposure to high altitude hypoxia leads to abnormal liver and kidney function and pathological changes in liver tissue. Astragaloside Ⅳ intervention can improve the liver's ability to resist oxidative stress damage in high altitude hypoxia,protect liver and kidney function in hypoxia,and improve the body's adaptability in high altitude hypoxia.
High altitude hypoxiaOxidative stressNrf2HO-1Liver and kidney functionAstragaloside Ⅳ