青蒿素对实验性自身免疫性重症肌无力大鼠R97-116抗体及细胞因子的影响

Influence of artemisinin on the expression of R97-116 antibody and cytokines in Lewis rats with experimental auto immune myasthenia gravis

目的探讨青蒿素(artemisinin)对实验性自身免疫性重症肌无力(EAMG)大鼠R97-116抗体及干扰素γ(IFN-γ)、白细胞介素17(IL-17)表达水平的影响。方法采用鼠源AChRα亚基97-116肽段免疫方法建立EAMG大鼠模型,将造模成功的大鼠20只随机分为青蒿素小、中、大剂量组和EAMG对照组。青蒿素小、中、大剂量组分别给予15、30、45mg/(kg·d)青蒿素溶液灌胃治疗,1次/d,模型对照组给予等浓度二甲基亚砜水溶液灌胃。评测各组大鼠体质量和临床症状,采用流式细胞术检测淋巴结单个核细胞悬液细胞因子IFN-γ、IL-17水平,ELISA法检测血清抗R97-116IgG/IgG1/IgG2b水平。结果青蒿素中、高剂量组大鼠体质量高于对照组(P<0.05);青蒿素各剂量组大鼠临床评分低于对照组(P<0.05)。青蒿素各治疗组IFN-γ、IL-17水平均低于对照组(P<0.01)。青蒿素15mg/(kg·d)剂量组血清IgG、IgG1、IgG2b水平与对照组比较差异无统计学意义(P>0.05);30mg/(kg·d)剂量组血清IgG(P<0.05)、IgG1(P<0.01)、IgG2b(P<0.01)水平低于对照组;45mg/(kg·d)剂量组血清IgG(P<0.05)、IgG1(P<0.01)水平低于对照组。结论青蒿素能改善EAMG大鼠临床症状,对EAMG大鼠具有免疫调节作用,其机制可能与其通过直接或间接降低血清抗R97-116抗体水平、抑制淋巴结单个核细胞分泌IFN-γ和IL-17促炎性因子有关。

Objective To investigate the influence of artemisinin on the expression of R97-116 antibody and interferon-gamma（IFN-γ）,interleukin-17（IL-17）in Lewis rats with experimental autoimmune myasthenia gravis（EAMG）.Methods EAMG models were established by subcutaneous injection of synthetic peptide R97-116 into both hind footpads of Lewis rats.Twenty rats were randomly divided into four groups：the artemisinin low,medium,high dose group and the control group（n=5in each group）.Artemisinin was administrated daily by oral gavage at a dose of 15mg/（kg·d）,30mg/（kg·d）and 45mg/（kg·d）,and the control group were administrated with dimethyl sulphoxide（DMSO）solution of the same concentration.Clinical symptoms and body weight were evaluated,the levels of intracellular cytokines IFN-γand IL-17 in mononuclear cell（MNC）were analyzed by flow cytometry,anti-R97-116IgG/IgG1/IgG2 b antibody in the serum were detected by ELISA.Results The rats′weights were significantly higher in the medium and high dose group of artemisinin than that of the control group（P0.05）.Each group of artemisinin exhibited lower clinical scores than the control group（P0.05）.The secretion of IFN-γin each group of artemisinin were lower than the control group（P0.01）,and so did IL-17.The levels of R97-116IgG/IgG1/IgG2 bwere not significantly different between the low dose group of artemisinin and the control group（P0.05）.The levels of serum R97-116 IgG,IgG1and IgG2 bin the medium dose group of artemisinin were lower than the control group（P0.05,P0.01,P0.01,respectively）.The levels of serum R97-116 IgG and IgG1 in the high dose group of artemisinin were lower than the control group（P0.05,P0.01,respectively）.Conclusions It is suggested that artemisinin could ameliorate EAMG by decreasing the level of anti R97-116 antibody in serum,down-regulating production of cytokines IFN-γand IL-17 in lymph node mononuclear cells.