补中益气汤改善CPZ诱导的脱髓鞘小鼠神经行为缺陷及促进髓鞘再生

Buzhong Yiqi Decoction improved neurobehavioral defects and promoted myelin regeneration in CPZ-induced demyelinating mice

目的:探究补中益气汤(BYD)对双环己酮草酰二腙(CPZ)诱导的脱髓鞘小鼠行为缺陷的改善作用及促进髓鞘再生的机制。方法:30只C57BL/6雄性小鼠随机分为对照组、模型组和BYD组,每组10只。对照组正常饲养,模型组和BYD组0.2%CPZ喂饲;第29日起,BYD组灌胃BYD,30 g/kg,2次/d,对照组和模型组灌胃等量生理盐水。第42日,各组进行旷场和高架十字迷宫试验检测行为学变化,取脑组织切片行TrueGold染色及MBP和GFAP免疫荧光染色,观察海马胼胝体髓鞘脱失情况;EILSA法检测小鼠脑组织中炎症相关细胞因子IL-6、IL-10、IL-1β和TNF-α表达水平。结果:与模型组比较,BYD组明显改善小鼠在迷宫和旷场试验中的运动活性及胼胝体髓鞘脱失,减少星形胶质细胞损伤,降低促炎细胞因子IL-6和IL-1β表达,提高抑炎细胞因子IL-10表达,差异均有统计学意义(P<0.05,P<0.01)。结论:BYD可能通过免疫调节,减轻脑组织炎症反应,改善CPZ模型小鼠的髓鞘再生及神经行为。

Objective:To explore the mechanism of improving behavior defect and promoting myelin regeneration in CPZ-induced demyelinating mice by Buzhong Yiqi Decoction(BYD).Methods:C57BL/6 male mice were randomly divided into control group,model group(CPZ)and Buzhong Yiqi decoction(BYD)group,with 10 mice in each group.The Control group was fed normally,the CPZ and BYD groups were fed 0.2%CPZ,and from the 29th day,the BYD group was given gavage(30 g/kg),and the Control and CPZ groups were given gavage with equal amount of normal saline,respectively.On the 42nd day,open field and elevated cross maze tests were performed to detect behavior.TrueGold staining,MBP staining and GFAP immunofluorescence staining were used to observe the myelin loss of hippocampal corpus callosum.The expression of inflammation-related cytokines IL-6,IL-10,IL-1βand TNF-αin brain tissue was detected by EILSA assay.Results:Compared with CPZ group,the mice in BYD group showed significantly improved motor activity in maze and open field and myelin loss of callosum detected by TrueGold staining(P<0.05),reduced astrocyte injury(P<0.05),decreased expression of pro-inflammatory cytokines IL-6 and IL-1β,and increased expression of anti-inflammatory cytokine IL-10(P<0.05).Conclusion:BYD may reduce brain inflammation and improve myelin regeneration and neurobehavior of CPZ model mice through immunomodulation.