Effect and mechanism of astragaloside Ⅳ on cerebral ischemia-reperfusion injury in rats
Objective To investigate the effect of astragaloside Ⅳ(AS-Ⅳ)on brain injury in cerebral ischemia-reperfusion(CI-RI)rats and its possible mechanism.Methods 65 rats were selected to establish cerebral ischemia-reperfusion model by middle cerebral artery occlusion thread occlusion(MCAO).The successful rats were randomly divided into model group,low,medium and high doses of AS-Ⅳ group,and another control group,with 12 rats in each group.The low,medium and high doses of AS-Ⅳ groups were gavaged with 20,40 and 80 mg·kg-1 AS-Ⅳ suspension(prepared with distilled water),respectively,and the control and model group were given the same amount of distilled water.The neurological deficit of rats was evaluated.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)were detected by enzyme linked immunosorbent assay(ELISA).The pathological changes of rat hippocampal were observed by HE staining.The mRNA and protein expressions of peroxisome proliferator receptor γ coactivator 1 α(PGC-1α)and nuclear factor E2 related factor 2(Nrf2)in rats hippocampus were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting.Results Compared with the model group,the levels of neurological Garcia JH score at each time,GSH-Px,SOD,PGC-1 and Nrf2 mRNA and protein expression were increased,the levels of TNF-α,IL-1β,IL-6 and MDA were decreased in low,medium and high doses of AS-Ⅳ groups(P<0.05).Compared with low dose of AS-Ⅳ group,the index levels medium and high doses of AS-Ⅳ groups changed significantly,especially in high doses of AS-Ⅳ group(P<0.05).Conclusion AS-Ⅳ can improve the neurological injury,reduce the level of oxidative stress and improve neuroinflammation in MCAO rats,possibly by activating PGC-1α/Nrf2 signaling pathway.
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