Protective mechanism of Xiaoxuming Decoction regulating NLRP3 against cuprizone induced injury in demyelinating mice
OBJECTIVE To explore the effect of Xiaoxuming Decoction(XD)on neuroinflammation induced by cuprizone(CPZ)in demyelinating mice.METHODS Forty C57BL/6 male mice were randomized into four groups of control,CPZ,XD1(low-dose)and XD2(high-dose)(n=10 each).Except for Control group,the other three groups received a daily diet of 0.2％CPZ for modeling.From Day 28,XD1 and XD2 groups received gavages of 30 g·kg-1,bid and 30 g·kg-1,tid XD while Control and CPZ groups equal amounts of physiological saline until Day 42.Murine behaviors were detected by an elevated cross maze.Luxol fast blue(LFB)stain and myelin basic protein(MBP)immunofluorescent stain were utilized for observing the loss of myelin sheath in corpus callosum.IBA1 stain of microglia in brain tissue was employed.mRNA and protein expression levels of CD11b,HMGB1,TLR4/NLRP3/Caspase-1 inflammasomes and inflammatory mediators were detected by fluorescent quantita-tive polymerase chain reaction(PCR)and Western blot.RESULTS As compared with CPZ model group,XD treatment group lowered the frequency of entering closed arm and distance of closed arm movement in mice,especially in high-dose treatment group(P＜0.05,P＜0.01),improved the demyelination of corpus callosum(P＜0.05)and minimized the infiltration of microg-lia in brain tissue(P＜0.05).XD treatment group down-regulated the mRNA/protein expressions of HMGB1,TLR4 and NLRP3 of inflammasomes(P＜0.05),decreased the mRNA of Caspase-1,IL-1β and IL-18(P＜0.05)and blunted Akt/NF-κB pathway activation(P＜0.05).CONCLUSION XD may play a neuroprotective role through regulating the expression of NLRP3 inflammasome,suppressing the activation and infiltration of microglia in brain tissue and minimizing neuroinflammatory injury in CPZ model.
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