桂枝茯苓丸对实验性自身免疫性脑脊髓炎小鼠的防治作用及机制研究

Preventive and therapeutic effect and its mechanism of Guizhi Fuling Pills on EAE mice

目的:探讨桂枝茯苓丸对实验性自身免疫性脑脊髓炎(EAE)小鼠的防治作用及可能机制。方法:建立EAE模型后,将C57BL/6雌性小鼠随机分为EAE对照组和桂枝茯苓丸高、中、低剂量组。免疫后第3天起,进行药物干预,直到免疫后第28天。每天记录各组小鼠体重变化和神经功能评分。第28天处死动物,观察EAE对照组和桂枝茯苓丸各组动物的脊髓和髓鞘的病理改变,ELISA法测定脾细胞上清液中细胞因子肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)的水平。结果:与EAE对照组比较,桂枝茯苓丸高、中、低剂量组均可减轻EAE症状,降低神经功能评分(P<0.01),抑制EAE小鼠体重丢失,以中剂量组效果最优。与EAE对照组比较,桂枝茯苓丸可明显抑制EAE小鼠脊髓炎性细胞浸润,减轻髓鞘脱失(P<0.05),抑制TNF-α、IL-6分泌(P<0.05,P<0.01)。结论:桂枝茯苓丸可改善EAE小鼠神经功能评分,明显抑制EAE小鼠脊髓炎性细胞浸润和减轻髓鞘脱失,其机制可能与抑制炎性细胞表达有关。

Objective:To explore the preventive effect and possible mechanism of Guizhi Fuling pills on experimental autoimmune encephalomyelitis(EAE)mice.Methods:After establishing the EAE model,C57BL/6 female mice were randomly divided into model group,Guizhi Fuling pills high,medium and low dose groups.From the third day after immunization,drug intervention was conducted until 28 days after immunization.Changes of body weight and neurological function scores of mice in each group were recorded every day.On the 28th day,the mice were sacrificed to observe the pathological changes of the spinal cord and myelin sheath in the EAE model group and Guizhi Fuling pills groups.Contents of TNF-α、IL-6 in supernatent of spleen cells were detected by ELISA.Results:Compared with the model group,the high,medium and low dose groups of Guizhi Fuling pills can delay the onset time of EAE mice,reduce the symptoms of EAE,decrease the neurological function score(P<0.01),and inhibit the weight loss of EAE mice.The medium dosage group has the best effect.Compared with the model group,the Guizhi Fuling pills can significantly inhibit the spinal inflammatory cell infiltration,reduce myelination in EAE mice(P<0.05)and inhibit the secretion of TNF-αand IL-6(P<0.05,P<0.01).Conclusion:Guizhi Fuling pills can improve the neurological function score of EAE mice,inhibit the infiltration of spinal inflammatory cells and reduce myelination in EAE mice through inhibiting inflammatory cell expression.