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首页|期刊导航|中国药理学通报|原花青素B2通过NRF2/HO-1/xCT/GPX4轴抑制氧化应激减轻H2O2诱导的人少突胶质细胞的损伤

原花青素B2通过NRF2/HO-1/xCT/GPX4轴抑制氧化应激减轻H2O2诱导的人少突胶质细胞的损伤OA北大核心CSTPCD

Proanthocyanin B2 inhibits oxidative stress and alleviates H2O2 induced damage to human oligodendrocytes through NRF2/HO-1/xCT/GPX4 axis

中文摘要英文摘要

目的 探讨原花青素B2(proanthocyanidins B2,PCB2)对过氧化氢(H2O2)诱导的人少突胶质细胞(MO3.13)氧化损伤和凋亡的保护作用及其机制.方法 筛选H2O2和PCB2的最佳作用浓度.分为正常组、PCB2组(100 mg.L-1 PCB2 处理 24 h)、H2O2 模型组(500 μmol·L-1 H2O2 处理24 h)、H2O2+PCB2 组(500 µmol·L-1 H2O2与 100 mg·L-1 PCB2共同处理24 h).FRAP法检测PCB2的抗氧化能力;CCK-8法检测各组细胞存活率,LDH法进行细胞毒性检测;微量酶标法和ELISA法检测各组细胞中LDH、NO、H2O2含量以及CAT、SOD活力;免疫荧光和Western blot分别检测各组细胞中NRF2、xCT、HO-1、Ferritin、GPX4的蛋白表达水平.亚铁离子荧光探针(FerroOrange)检测细胞内亚铁离子(Fe2+)含量.结果 H2O2能诱导MO3.13氧化损伤并导致细胞铁死亡,PCB2能够减轻MO3.13氧化损伤和铁死亡;与H2O2模型组相比,PCB2干预能够明显升高MO3.13内LDH含量,降低NO、H2O2含量,提高SOD、CAT活力;上调NRF2、xCT、HO-1、Ferritin、GPX4的蛋白表达水平.结论 PCB2能够通过NRF2/HO-1/xCT/GPX4轴增强细胞抗氧化能力,减轻H2O2诱导的MO3.13氧化损伤.

Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.

刘健;王青;陈莹;梁亚杰;蒲萌;张紫薇;郑璐璐;柴智;肖莹;马存根

山西中医药大学国家中医药管理局多发性硬化益气活血重点研究室,神经生物学研究中心,山西晋中 030619||湖北省武汉市蔡甸区人民医院,湖北武汉 430100山西中医药大学国家中医药管理局多发性硬化益气活血重点研究室,神经生物学研究中心,山西晋中 030619湖北省武汉市蔡甸区人民医院,湖北武汉 430100

中医学

原花青素B2MO3.13H2O2氧化损伤NRF2/HO-1/xCT/GPX4轴铁死亡

proanthocyanin B2MO3.13H2O2ox-idative damageNRF2/HO-1/xCT/GPX4 axisferrop-tosis

《中国药理学通报》 2024 (009)

1735-1743 / 9

国家青年科学基金资助项目(No 81903596);山西省回国留学人员科研资助项目(No 2022-165);国家中医药管理局科研课题(No 2023ZYYDA2038);山西省卫健委医学科技领军团队(No 2020TD05);山西省中医药管理局科研课题(No 2023ZYYB040);山西省卫健委2022年度中医药科研课题立项计划(No 2022ZYYC090);山西中医药大学学科建设经费(No 2024XKJS-02);山西省教育厅科技创新项目(No 2022L336);山西中医药大学2022年度科技创新团队(No 2022TD2006);山西中医药大学科技创新能力培育计划(No 2022-TY-PH-11,2022-TY-PH-37)

10.12360/CPB202404039

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