中国病理生理杂志2025，Vol.41Issue(4)：743-749,7.DOI:10.3969/j.issn.1000-4718.2025.04.014
基于Nrf2/HO-1/GPX4通路探讨参黄冲剂对Aβ25-35诱导的HT22细胞铁死亡的影响
Effects of Shen-Huang granule on Aβ25-35-induced ferroptosis of HT22 cells via Nrf2/HO-1/GPX4 pathway
摘要
Abstract
AIM:To investigate the effect and mechanism of Shen-Huang granule(SHG)on Aβ25-35-induced ferroptosis in HT22 cells.METHODS:An in vitro model of Alzheimer disease(AD)was established by treating HT22 cells with Aβ25-35.The cells were divided into the following groups:control group,model group(Aβ25-35 group),ferroptosis inhibitor ferrostatin-1(Fer-1)group,low-dose SHG(SHG-L)group,and high-dose SHG(SHG-H)group.Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay.Ultrastructural changes in each group were observed via trans-mission electron microscopy.The intracellular levels of reactive oxygen species(ROS)were measured by flow cytometry.Iron deposition and lipid peroxidation levels were evaluated by examining Fe2+,total superoxide dismutase(SOD),and malondialdehyde(MDA)levels.Western blot analysis was employed to detect the protein expression of cyclooxygenase 2(TfR1),ferritin heavy chain 1(FTH1),nuclear factor E2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).RE-SULTS:Compared to the control group,the model group exhibited mitochondrial shrinkage,increased membrane densi-ty,and decreased cristae.Levels of ROS,Fe2+,and MDA were significantly elevated,while SOD levels were markedly re-duced.The protein expression of SLC7A11,GPX4,FTH1,Nrf2,and HO-1 was significantly down-regulated,whereas the expression of COX2 and TfR1 was significantly up-regulated.In comparison to the model group,the morphology and structure of mitochondria improved in the Fer-1,low-dose SHG,and high-dose SHG groups.ROS,Fe2+,and MDA levels decreased while SOD levels increased.Furthermore,the expression of SLC7A11,GPX4,FTH1,Nrf2,and HO-1 was sig-nificantly up-regulated,while COX2 and TfR1 expression was significantly down-regulated.CONCLUSION:Shen-Huang granule can inhibit Aβ25-35-induced ferroptosis in HT22 cells,and the underlying mechanism may involve the Nrf2/HO-1/GPX4 signaling pathway.关键词
参黄冲剂/阿尔茨海默病/铁死亡/Nrf2/HO-1/GPX4通路/HT22细胞Key words
Shen-Huang granule/Alzheimer disease/ferroptosis/Nrf2/HO-1/GPX4 signaling pathway/HT22 cells分类
临床医学引用本文复制引用
王晓涵,刘梦雨,张雅涵,胥瑞杰,赵悦潼,韩旭..基于Nrf2/HO-1/GPX4通路探讨参黄冲剂对Aβ25-35诱导的HT22细胞铁死亡的影响[J].中国病理生理杂志,2025,41(4):743-749,7.基金项目
江苏省自然科学基金项目(No.BK20231378) （No.BK20231378）
南京市医疗机构中药传统制剂研究项目(No.NJCC-ZJ-202306) （No.NJCC-ZJ-202306）
江苏省卫生健康委员会老年医学临床技术应用研究项目带头人科研项目(No.LR2022002) （No.LR2022002）
江苏省中医药科技发展专项计划(No.2020ZX08) （No.2020ZX08）
