Ameliorative effect of norwogonin on brain tissue injury induced by acute hypobaric hypoxia
OBJECTIVE To explore the effects and mechanisms of norwogonin(Now)in ameliorating brain tissue injury induced by acute hypobaric hypoxia(AHH)in mice.METHODS A total of 78 male BALB/c mice were randomized into six groups of normal control,HH,rutin(200 mg·kg-1),low-dose(50 mg·kg-1),medium-dose(100 mg·kg-1)and high-dose(200 mg·kg-1)norwogonin.Drugs were administered by an intraperitoneal injection in normal control group.HH groups received saline intraperitoneally.Mice were exposed to a low-oxygen chamber at a simulated altitude of 8 000 m for 24 h for modeling of AHH-induced brain tissue injury.Hematoxylin eosin(HE)stain was utilized for assessing pathological changes.The levels of hydrogen peroxide(H2O2),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in brain tissues were measured for assessing the state of oxidative stress.Enzyme-linked immunosorbent assay(ELISA)was employed for detecting the levels of interleukin-1β(IL-1β),tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in brain tissues for assessing inflammatory responses.Western blot was utilized for quantifying the expression levels of hypoxia-related proteins[hypoxia-inducible factor-1α(HIF-1α)& vascular endothelial growth factor(VEGF)],antioxidative stress-related proteins[nuclear factor erythroid 2-related factor 2(Nrf2)& heme oxygenase 1(HO-1)],inflammation-related proteins[nuclear factor kappa-B(NF-κB)& TNF-α]and apoptosis-related proteins[Bcl-2-associated X protein(Bax)&B cell lymphoma 2(Bcl-2)& cleaved cas-pase-3].RESULTS As compared with control group,brain tissues of HH group showed some pathological changes.The levels of H2O2,MDA,IL-1β,TNF-α and IL-6 rose markedly while the levels of SOD and GSH declined significantly.Also the expres-sions of VEGF,Nrf2,HO-1,NF-κB,TNF-α,Bax and cleaved caspase-3 were elevated,the expression of Bcl-2 dropped and the ratio of Bax/Bcl-2 spiked.Norwogonin pretreatment reversed these changes.CONCLUSION Norwogonin alleviates AHH-induced brain tissue injury in mice through suppressing oxidative stress,inflammatory responses and apoptosis.
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