时珍国医国药2026，Vol.37Issue(18)：3466-3473,8.DOI:10.70976/j.1008-0805.SZGYGY-2026-1809
黄芪甲苷从Nrf2/SLC7A11/GPX4通路抑制铁死亡改善大鼠脊髓缺血再灌注损伤的研究
Astragaloside Ⅳ alleviates spinal cord ischemia-reperfusion injury in rats by inhibiting ferrop-tosis via the Nrf2/SLC7A11/GPX4 pathway
摘要
Abstract
Objective To investigate the effect of Astragaloside Ⅳ(AS-Ⅳ)on spinal cord ischemia-reperfusion injury(SCII)in rats and its underlying mechanism.Methods Sixty SD rats were randomly divided into five groups:sham,SCII,AS-Ⅳ high/low-dose(AS-IVH/L),and methylprednisolone(MP).Except for the sham group,all other groups underwent SCII modeling using the modified Zivin's method.Corresponding drug interventions were administered intraperitoneally once at 2 h after surgery.The sham group underwent laparotomy and abdominal aortic isolation without occlusion.Neurological function was assessed using the Basso,Beattie,Bresnahan(BBB)locomotor rating scale at 24 h post-surgery,after which the L2-5 spinal cord segments were harvested.Spinal cord morphology and neuronal survival were observed by HE and Nissl staining.The activities of SOD and CAT,and the levels of MDA,LPO,ferrous ion(Fe2+),and 8-hydroxy-2'-deoxyguanosine(8-OHdG)were measured using commercial assay kits.The protein expression of acyl-CoA synthetase long-chain family member 4(ACSL4)and glutathione peroxidase 4(GPX4)was detected by immunohistochemistry(IHC).The protein and mRNA expression levels of Keap1,Nrf2,HO-1,GPX4,and SLC7A11 were determined by Western blot(WB)and quantitative real-time polymerase chain reaction(qRT-PCR),respectively.Results Compared with the sham group,rats in the SCII group exhibited significantly lower BBB scores,reduced neuronal count,and evident pathological damage including edema and necrosis in spinal cord tissue.The activities of SOD and CAT were markedly decreased,while the contents of MDA,LPO,Fe2+,and 8-OHdG were increased.The expression of the ferroptosis marker ACSL4 was up-regulated,whereas GPX4 was down-regulated at the pro-tein level.Furthermore,WB analysis showed that the protein expression of Keap1 and cytosolic Nrf2 was increased,while that of nuclear Nrf2,HO-1,SLC7A11,and GPX4 was decreased.Consistently,qRT-PCR revealed decreased mRNA levels of Nrf2,HO-1,SLC7A11,and GPX4,and an increased mRNA level of Keap1(all P<0.05 or P<0.01).Treatment with either AS-Ⅳ or MP signifi-cantly reversed these changes induced by SCII.Conclusion Astragaloside Ⅳ alleviates spinal cord ischemia-reperfusion injury in rats,likely by suppressing ferroptosis through activation of the Nrf2/SLC7A11/GPX4 signaling pathway.关键词
脊髓缺血再灌注损伤/黄芪甲苷/铁死亡/Nrf2/SLC7A11/GPX4Key words
Spinal cord ischemia-reperfusion injury/Astragaloside Ⅳ/Ferroptosis/Nrf2/SLC7A11/GPX4 pathway分类
医药卫生引用本文复制引用
陈元平,张翔,周伟,周立亚..黄芪甲苷从Nrf2/SLC7A11/GPX4通路抑制铁死亡改善大鼠脊髓缺血再灌注损伤的研究[J].时珍国医国药,2026,37(18):3466-3473,8.基金项目
湖北省卫健委中医药科研项目(ZY2021M050) （ZY2021M050）
