补阳还五汤通过NCOA4/FTH1通路抑制铁死亡改善缺血性脑血管病大鼠的脑组织损伤OA

Objective:To investigate the mechanism of Buyang Huanwu decoction in improving brain tissue injury in rats with ischemic cerebrovascular disease based on ferroptosis mediated by NCOA4/FTH1 sig-naling pathway.Methods:The SD rats were randomly divided into sham operation group(n=14),model group(n=17),ferroptosis inhibitor Ferrostatin-1 group(n=15),and Buyang Huanwu decoction group(n=15),Buyang Huanwu decoction+ferroptosis inducer Erastin group(n=15).A rat model of ischemic cere-brovascular disease was established by wire plug method.The Longa method was used to evaluate the neuro-logical function of rats in each group.TTC staining was used to detect the volume of cerebral infarction.HE staining was used to detect pathological damage in brain tissue.The levels of malondialdehyde(MDA),gluta-thione(GSH)and Fe2+in the cerebral ischemic penumbra tissues of rats in each group were detected.Immu-nohistochemical staining assay was used to detect the expression of glutathione peroxidase 4(GPX4)protein in the penumbra zone tissue of cerebral ischemia.The mRNA and protein expressions of nuclear receptor coac-tivator 4(NCOA4)and ferritin heavy chain 1(FTH1)in cerebral ischemic penumbra tissues were detected by RT-qPCR and Western blot.Results:Compared with the sham operation group,the neurological function score of the rats in the model group increased(P＜0.05),cerebral infarction volume increased(P＜0.05),cells in the brain tissue of the ischemic penumbra region were damaged,the MDA,Fe2+and NCOA4 in the pe-numbra tissues of cerebral ischemia increased(P＜0.05),and the GSH,GPX4 and FTH1 in the penumbra tissue of cerebral ischemia increased(P＜0.05).Compared with the model group,the neurological function score of the ferroptosis inhibitor group and the Buyang Huanwu decoction group decreased(P＜0.05),cerebral infarction volume decreased(P＜0.05),the damages in the penumbra tissues of cerebral ischemia reduced,the MDA,Fe2+and NCOA4 in the penumbra tissues of cerebral ischemia decreased(P＜0.05),and the GSH,GPX4 and FTH1 in the penumbra tissue of cerebral ischemia increased(P＜0.05).Erastin inhibited the effect of Buyang Huanwu decoction on rats with ischemic cerebrovascular disease in a certain extent(P＜0.05).Conclusion:Buyang Huanwu decoction improves the brain tissue injury of rats with ischemic cerebro-vascular disease by alleviating the pathological changes of brain tissue in cerebral infarction and ischemic pe-numbra zone,and the mechanism may be achieved by inhibiting the expression of NCOA4 and promoting the expression of FTH1 to regulate the NCOA4/FTH1 signaling pathway,thereby inhibiting ferroptosis.