淫羊藿苷调控星形胶质细胞极化抑制CPZ诱导的小鼠髓鞘脱失OA

AIM:To investigate the effects of icariin(ICA)on cuprizone(CPZ)-induced demyelination in mice through the regulation of astrocyte(AST)polarization.METHODS:Twenty-four male C57BL/6 mice were random-ly divided into control(CON),CPZ,and ICA groups,with eight mice in each group.Myelin integrity was assessed using TrueGold staining.The levels of myelin basic protein(MBP),the A1 phenotype AST marker C3 and its derived factors chemokine(C-X-C motif)ligand 10(CXCL10)and CXCL1,as well as the A2 phenotype AST marker S100A10 and its derived factors fibroblast growth factor 2(FGF2)and ciliary neurotrophic factor(CNTF),were detected by immunofluo-rescence staining.The expression of MBP and S100A10 was analyzed by Western blot,while the levels of tumor necrosis factor-α(TNF-α),interleukin-1α(IL-1α)and brain-derived neurotrophic factor(BDNF)were measured using ELISA.Primary ASTs were divided into CON,cytokine(CYK),and ICA intervention groups.The expression of C3,S100A10,CXCL10,and FGF2 was examined by immunofluorescence staining,and the levels of CXCL1,CXCL10,FGF2,and BDNF were detected by ELISA.RESULTS:The CPZ group showed marked demyelination in the corpus callosum(P<0.01),accompanied by elevated expression of both A1 and A2 AST markers and their associated factors(P<0.05 or P<0.01).After ICA administration,the levels of C3,CXCL10,CXCL1,FGF2,TNF-α,and IL-1α were significantly de-creased,while S100A10,CNTF,and BDNF levels showed no marked differences compared with the CPZ group(P>0.05).In the cell experiments,cytokine exposure(CYK group)resulted in a substantial increase in A1-type astrocyte markers and their associated factors(P<0.05),whereas the expression of A2-type markers and their derivatives was mark-edly reduced(P<0.05 or P<0.01).After ICA treatment,C3 expression did not change significantly(P>0.05),but CX-CL10 and CXCL1 levels were markedly reduced(P<0.01).In contrast,S100A10 and BDNF were notably increased(P<0.01),and FGF2 expression remained unchanged(P>0.05).CONCLUSION:Icariin facilitated remyelination in mouse brain tissue by suppressing the pro-inflammatory A1 astrocyte phenotype and promoting the neuroprotective A2 phe-notype,thereby improving the inflammatory microenvironment and mitigating CPZ-induced demyelination.