Mechanism of proanthocyanidin B2 regulating iron metabolism and reducing oxidative stress to promote myelin regeneration in cuprizone-induced demyelinating model
Objective:To explore the mechanism of proanthocyanidin B2(PC-B2)promoting myelin regeneration in a mouse demyelination model induced by cuprizone(CPZ).Methods:Forty C57BL/6 male mice were randomly divided into four groups and given 0.2%(mass fraction)CPZ to construct a demyelinating mouse model.The behavioral changes of mice were observed by open field,T maze and elevated plus maze.The changes of myelin sheath,MBP,dMBP,CC1,ferritin,GFAP and Iba1 in corpus callosum were observed by LFB and immunofluorescence staining.The expression levels of CAT,MDA,ROS,SOD,GSH-Px,ferrous ion and total iron in brain homogenate were detected by ELISA.RT-PCR and Western blot were used to detect the expression of TfR1,NCOA4,ferritin,FPN1,GPX4,and Nrf2/HO-1 pathway.Results:Compared with CPZ +NS group,PC-B2 could promote the regeneration of myelin in the corpus callosum region,improve the abnormal iron metabolism and lipid peroxidation induced by CPZ,and enhance the activities of CAT,SOD and GSH-Px.PC-B2 increased the numbers of oligodendrocytes and astrocytes and decreased the number of microglia.At the same time,the expression of TfR1 and NCOA4 was decreased,and the expression of ferritin,FPN1,GPX4 and Nrf2/HO-1 was increased.Conclusion:PC-B2 may improve iron metabolism disorders and oxidative stress in the brain of CPZ mice by activating the Nrf2/HO-1 signaling pathway and play a role in myelin repair.
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