山东科学2024，Vol.37Issue(4)：34-44,11.DOI:10.3976/j.issn.1002-4026.20230170
肝豆灵片通过调控PKCβⅡ/ACSL4/ALOX5信号通路改善肝豆状核变性铁死亡的机制
The mechanism by which Gandouling tablets improve ferroptosis in hepatolenticular degeneration through PKCβⅡ/ACSL4/ALOX5 signaling pathway regulation
摘要
Abstract
This study investigates the effects of Gandouling(GDL)tablets on ferroptosis in hepatolenticular degeneration in TX mice and their mechanism of action on the ferroptosis of HT22 cells induced by CuCl2,based on the PKCβⅡ/ACSL4/ALOX5 signaling pathway.TX mice were divided into five groups:control,model,GDL tablet,Fer-1,and Glutathione.HT22 cells were also divided into five groups:control,model,GDL tablet,Fer-1,and GDL tablet+Fer-1.Hematoxylin and eosin staining was used to detect the pathological changes in the hippocampus tissues of the mice.Western blotting was used to detect the expression of PKCβⅡ,ACSL4,and ALOX5 in the hippocampus tissues and HT22 cells of the mice,as well as the expression of SLC7A11 and GPX4 in HT22 cells.The content of Fe2+in the hippocampus tissues of the mice was detected via microassay.The levels of SOD,MDA,and GSH-Px in HT22 cells were detected by microplate assay.Finally,the expression of PKCβⅡ,ACSL4,and ALOX5 mRNA in HT22 cells was detected by quantitative real-time polymerase chain reaction.Compared with the control group,the hippocampus tissues of mice in the model group showed clear damage;the protein expression of PKCβⅡ,ACSL4,and ALOX5 showed a clear increase;the protein expression of SLC7A11 and GPX4 decreased significantly;and Fe2+content increased significantly(P<0.05).Compared with the model group,the pathological damage to hippocampus tissues showed improvements in the GDL tablet,Fer-1,and Glutathione group with the effects being noticeable in the GDL tablet group.It was possible to inhibit ferroptosis of HT22 cells in the GDL tablet and Fer-1 group and significantly lower their expression of PKCβⅡ,ACSL4,and ALOX5 protein and mRNA in comparison to the model group(P<0.05).The MDA contentalso decreased significantly(P<0.05)while the SOD activity and the GSH-Px content increased significantly(P<0.05).Thus,GDL tablets can inhibit ferroptosis in hippocampus tissues of TX mice andinhibit ferroptosis induced by CuCl2 in HT22 cells.Moreover,the ferroptosis mechanism may be related to the down-regulation of the PKCβⅡ,ACSL4,and ALOX5 signaling pathway and the attenuation of intracellular lipid peroxidation.关键词
肝豆灵片/肝豆状核变性/PKCβⅡ/ACSL4/ALOX5信号通路/铁死亡/机制Key words
Gandouling tablets/hepatolenticular degeneration/PKCβⅡ/ACSL4/ALOX5 signaling pathway/ferroptosis/mechanism of action分类
中医学引用本文复制引用
吴博进,董婷,闻雨雅,田丽伟,赵晨玲..肝豆灵片通过调控PKCβⅡ/ACSL4/ALOX5信号通路改善肝豆状核变性铁死亡的机制[J].山东科学,2024,37(4):34-44,11.基金项目
安徽高校研究生科学研究项目(YJS20210476) （YJS20210476）
安徽省自然科学基金(2208085MH270) （2208085MH270）
安徽高校自然科学研究项目(KJ2021A0547) （KJ2021A0547）
安徽中医药大学第一附属医院临床科学研究项目(2020yfyzc01) （2020yfyzc01）
国家自然科学基金(82205076) （82205076）
安徽中医药大学科技创新基金(2021ZC08) （2021ZC08）
