中国中药杂志2026，Vol.51Issue(2)：553-564,12.DOI:10.19540/j.cnki.cjcmm.20251021.901
脑泰方通过Nrf2调控抑制神经元铁死亡与焦亡减轻脑缺血再灌注损伤
Naotaifang alleviates cerebral ischemia-reperfusion injury by inhibiting neuronal ferroptosis and pyroptosis through Nrf2 regulation
摘要
Abstract
This study aims to investigate the effects of Naotaifang(NTF)on neuronal ferroptosis and pyroptosis in cerebral ischemia-reperfusion injury(CIRI),with a focus on nuclear factor erythroid 2-related factor 2(Nrf2).A rat model of CIRI was established by middle cerebral artery occlusion/reperfusion(MCAO/R).Sprague-Dawley rats were randomly assigned to a sham group,a model group,low/medium/high-dose(4.5,9,18 g·kg-1,respectively)NTF groups,and a butylphthalide(60 mg·kg-1)group(n=15 per group).After modeling,the treatment groups received corresponding agents by gavage once daily for 7 days,and the sham and model groups received an equal volume of normal saline.After treatment,the neurological function was assessed based on the Zea-Longa score,the infarct volume by TTC staining,and cellular morphology by HE staining.The levels of Fe2+,interleukin-1β(IL-1β),and interleukin-18(IL-18)were measured by ELISA,and those of malondialdehyde(MDA)and glutathione(GSH)by biochemical assays.Western blot was employed to examine the expression levels of Nrf2,glutathione peroxidase 4(GPX4),NOD-like receptor family pyrin domain-containing 3(NLRP3),and the N-terminal fragment of gasdermin D(GSDMD-N).In the cell experiment,oxygen-glucose deprivation/reperfusion(OGD/R)was used to model CIRI in SH-SY5Y cells.siRNA-mediated Nrf2 knockdown(si-Nrf2)was employed to probe into the role of Nrf2 in OGD/R-induced ferroptosis and pyroptosis and the intervention effect of NTF.Membrane damage was evaluated by Hoechst/propidium iodide staining and LDH release,and GPX4 and GSDMD immunofluorescence was employed to indicate ferroptosis and pyroptosis,respectively.Fe2+,MDA,and GSH were quantified biochemically,and the levels of IL-1β and IL-18 by ELISA.The expression of Nrf2,GPX4,NLRP3,and GSDMD-N was quantified by Western blot.The cellular ultrastructure was observed by transmission electron microscopy.The results of the animal experiment showed that NTF promoted the expression of Nrf2 to alleviate neuronal ferroptosis and pyroptosis,thus producing significant neuroprotection against CIRI in a dose-dependent manner.The results of the cell experiment showed that the neuroprotective effects of NTF after CIRI were mediated by Nrf2-dependent suppression of neuronal ferroptosis and pyroptosis.Taken together,NTF attenuates CIRI by suppressing neuronal ferroptosis and pyroptosis through Nrf2-mediated regulation.关键词
脑泰方/脑缺血再灌注损伤/Nrf2/铁死亡/焦亡Key words
Naotaifang/cerebral ischemia-reperfusion injury/Nrf2/ferroptosis/pyroptosis引用本文复制引用
王文凤,廖君,张秀丽,聂慧芳,杨彤,刘欣艾,梅志刚,葛金文..脑泰方通过Nrf2调控抑制神经元铁死亡与焦亡减轻脑缺血再灌注损伤[J].中国中药杂志,2026,51(2):553-564,12.基金项目
国家自然科学基金面上项目(82174167) （82174167）
国家自然科学基金青年项目(82405157) （82405157）
湖南省教育厅科学研究项目(24B0365) （24B0365）
湖南中医药大学校级科研项目(2022XJZKC007) （2022XJZKC007）
湖南省大学生创新训练项目(S202510541076) （S202510541076）
