Intervention Effect of Dabufei Decoction(大补肺汤)on Acute Brain Injury in Rats with High-Altitude Hypoxia Based on Keap1-Nrf2 Signaling Pathway
Objective:To investigate the intervention effect of Dabufei decoction(大补肺汤)on brain injury in rats with high-altitude hypoxia by regulating the expression of Kelch-like ECH-associated protein 1(Keap1)/nuclear factor erythroid 2 related factor 2(Nrf2)signaling pathway and associated molecules.Methods:Sixty SPF grade SD rats were randomly divided into normal control group,model group,dexamethasone 0.5 mg/kg group,Dabufei decoction 8.8,17.6 and 35.1 g/kg groups.After adapting feeding for 3 days,the rats in Dabufei decoction were given corresponding drugs by intragastric administration for 14 days.The rats in dexamethasone group received the drugs by intraperitoneal in-jection for 3 consecutive days before entering the chamber,and the rats in other groups were given the same volume of normal saline.Except for normal control group,from the 15th day,the rats in each group were exposed to hypoxia in the hypobaric chamber for experimental animals for 3 consecutive days.The animals were sacrificed at the end of modeling,and HE staining was conducted to observe the morphology of the hippocampus.The malondialdehyde(MDA)content,glutathione peroxidase(GSH-Px)activity,and glutathione(GSH)content in the brain tissue were detected by the TBA method,colorimetric method,and microplate method,respectively.Western blotting(WB)and RT-qPCR were used to detect the protein and mRNA expressions of Keap1,Nrf2,Heme oxygenase-1(HO-1)and quinone oxidoreductase L(NQO-1)in the brain tissue of rats.Results:HE results showed that in model group,the pyramidal cells in the CA1 region of the hippocampus were ar-ranged irregularly and swollen,with loose and light stained cytoplasm.Compared with normal control group,the activity of GSH-Px and the content of GSH were significantly decreased(P＜0.01,P＜0.05),while MDA content was significantly increased(P＜0.01)in the brain of the model group.The protein and mRNA expressions of Nrf2,HO-1,NQO-1,and Keap1 were significantly up regulated(P＜0.05 or P＜0.01)in the brain of the model group.Compared with the model group,the pyramidal cells in the hippocampal CA1 region were compactly arranged with clear boundary,and cell swelling was alleviated in Dabufei decoction groups.The MDA content was decreased(P＜0.01),the GSH-Px activity and GSH content were significantly increased(P＜0.01,P＜0.05),the protein and mRNA expressions of Nrf2,HO-1,and NQO-1 were significantly up regulated,while the Keap1 expression was significantly down regulated(P＜0.01,P＜0.05).Conclusion:Dabufei decoction has a protective effect on brain injury of the rats with high-altitude hypoxia by regulating the Keap1-Nrf2 signaling pathway and reducing oxi-dative stress in brain tissues.
万方数据
维普
