基于JAK2/STAT3信号通路探讨远志散对双环己酮草酰二脘诱导的急性脱髓鞘小鼠模型的保护作用OA

Objective:To investigate the protective effect of Yuanzhi San(YZS,Milkwort Root Powder)on acute demy-elination of the central nervous system(CNS)induced by cuprizone(CPZ)via the JAK2/STAT3 signaling pathway in mice.Methods:Thirty male C57BL/6N mice were randomly divided into control group,model group,and YZS group,with 10 mice in each group.The control group was fed a standard diet,while the model and YZS groups were fed biscuits containing 0.2%CPZ for 6 weeks to establish the model.From the fifth week onward,the YZS group was administered YZS at a dose of 12 g/(kg.d)by gavage for 1 week,while the other two groups received an equal volume of saline for 1 week.The elevated plus maze test and open field test were used to assess anxiety-like behavior.Brain tissues were collected for black gold staining to observe myelin changes in the corpus callosum.Immunofluorescence staining was employed to detect the average fluorescence inten-sity of myelin basic protein(MBP),degraded MBP(dMBP),glial fibrillary acidic protein(GFAP),Janus kinase 2(JAK2),and signal transducer and activator of transcription 3(STAT3)in the brain tissues of the three groups.Western blot was used to measure the protein expression levels of JAK2 and STAT3.ELISA was performed to determine the levels of IL-1β,TNF-α,IL-6,and IL-10 in the brain tissues.Results:Compared with the control group,the model group showed an increase in the number of entries into the open arms,a decrease in the total distance moved in the closed arms,and an increase in the number of entries and total distance in the center area of the open field(P<0.01).Massive myelin loss was observed in the corpus callosum,with reduced MBP protein expression and enhanced expression of dMBP,GFAP,JAK2,and STAT3(P<0.01).The levels of pro-inflammatory cytokines(IL-1β,TNF-α,IL-6)were significantly elevated,while the anti-inflammatory cytokine IL-10 was significantly decreased(P<0.01).Compared with the model group,the YZS group exhibited improved behavioral performance,with reduced entries into the open arms,increased distance in the closed arms,and de-creased entries and distance in the center area(P<0.01).Myelin loss in the corpus callosum was attenuated,MBP expression was enhanced,and the expressions of dMBP,GFAP,JAK2,and STAT3 was suppressed(P<0.01).The levels of IL-1β,TNF-α,and IL-6 were significantly reduced,while IL-10 was significantly increased(P<0.01).Conclusion:Yuanzhi San has a protective effect on CPZ-induced acute demyelination in mice,and its mechanism may be related to the inhibition of inflam-matory response via suppressing the JAK2/STAT3 signaling pathway.