瞿麦治疗小鼠实验性自身免疫性神经炎的疗效及机制研究  

Study of the therapeutic effect and mechanism of Qumai on mice with experimental autoimmune neuritis

作　　者：乔保俊 周树虎[1] 郑培兵 齐子有 邢春叶 石其光 郝延磊[1] QIAO Baojun;ZHOU Shuhu;ZHENG Peibing;QI Ziyou;XING Chunye;SHI Qiguang;HAO Yanlei(Department of Neurology,Affiliated Hospital of Jining Medical University,Jining Shandong,272100,China)

机构地区：[1]济宁医学院附属医院神经内,272100 [2]济宁医学院,272100

出　　处：《中国神经免疫学和神经病学杂志》2018年第6期420-423,438,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：济宁市中医药科技发展计划项目(ZYY2015026);济宁市科技发展计划项目(济科字[2016]56号-120);国家自然科学基金资助项目(81771360).

摘　　要：目的观察瞿麦对实验性自身免疫性神经炎(EAN)小鼠临床症状、辅助性T淋巴细胞(Th)亚群、炎性细胞因子的影响,并探讨其改善EAN小鼠临床症状的可能机制。方法利用人工合成的P0180-199肽段混以完全福氏佐剂主动免疫C57BL/6小鼠建立EAN模型。将小鼠随机分为瞿麦治疗组和对照组,利用行为学评分进行疗效评估,流式细胞术检测外周血Th1、Th2、Th17、Treg细胞水平及Th1/Th2、Th17/Treg比值变化,采用ELISA法检测血清肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)和γ干扰素(IFN-γ)水平变化。结果与对照组比较,瞿麦治疗组EAN达峰时间明显延迟,对照组小鼠行为学评分在免疫后第17天达高峰,瞿麦治疗组为免疫后第19天,瞿麦治疗组小鼠达峰时行为学评分低于对照组(3.75±0.88 vs.4.75±0.46,t=2.828,P=0.013)。免疫后第28天瞿麦治疗组小鼠行为学评分仍低于对照组(0.44±0.41 vs.1.06±0.68;t=2.220,P=0.043)。与对照组相比,瞿麦治疗组外周血单个核细胞Th1/Th2比值(1.50±0.62 vs.1.61±0.09)和Th17/Treg细胞比值(0.21±0.04 vs.1.20±0.13)降低(P<0.01或P<0.05),血清TNF-α[(211.00±10.77)pg/mL vs.(244.29±21.52)pg/mL]、IL-1β[(109.29±4.74)pg/mL vs.(120.29±11.90)pg/mL]和IFN-γ[(707.71±4.23)pg/mL vs.(723.00±15.00)pg/mL]水平明显下降(P<0.01或P<0.05)。结论瞿麦可显著改善EAN小鼠模型的临床症状,其机制可能与影响Th细胞亚群比例、炎性细胞因子的表达有关,有望成为临床治疗吉兰-巴雷综合征/EAN的新策略。Objective To observe the effects of Qumai on clinical symptoms,Th cell subsets,inflammatory cytokines in mice with experimental autoimmune neuritis(EAN).Methods EAN model was established by actively immunizing C57BL/6 mice with synthetic P0 180-199 peptide and Freund s complete adjuvant.The mice were randomly divided into a Qumai group and a normal saline group.The efficacy of Qumai on EAN mice was assessed using behavioral score,the numbers of Th1,Th2,Th17,Treg cells and ratio of Th1/Th2,Th17/Treg cells in peripheral blood detected by flow cytometry,and the expression levels of TNF-α,IL-1βand IFN-γmeasured by ELISA.Results The peak time of EAN in the treatment group was significantly delayed.The behavior score of the control group reached its peak on the 17th day after immunization,which was shorter than the treatment group(on the 19 th day).The peak behavior score of the treatment group was lower than that of the control group(3.75±0.88 vs.4.75±0.46;t=2.828,P=0.013)On the 28th day after immunization,the behavioral score of the Qumai treatment group was still lower than that of the control group(0.44±0.41 vs.1.06±0.68;t=2.220,P=0.043).Compared with the control group,the Th1/Th2 ratio of peripheral blood mononuclear cells(1.50±0.62 vs.1.61±0.09)and Th17/Treg cell ratio(0.21±0.04 vs.1.20±0.13)decreased(P<0.01 or P<0.05),serum TNF-alpha[(211.00±10.77)pg/mL vs.(244.29±21.52)pg/mL],IL-1 beta[(109.29±4.74)pg/mL vs.(120.29±11.90)pg/mL]and IFN-gamma[(707.71±4.23)pg/mL vs.(723.00±15.00)pg/mL]decreased significantly(P<0.01 or P<0.05).Conclusions Qumai can significantly improve the clinical symptoms of the EAN mouse model.The mechanism maybe related to changes of Th cell subsets,inflammatory cytokines.Qumai is expected to become a new strategy for the clinical treatment of GBS/EAN.

关 键 词：瞿麦 神经炎 自身免疫性 实验性 格林-巴利综合征 T淋巴细胞 T淋巴细胞 调节 细胞因子类 

分 类 号：R744.5[医药卫生—神经病学与精神病学]