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山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (4): 11-16.doi: 10.6040/j.issn.1671-7554.0.2015.796

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AG490对实验性自身免疫性重症肌无力大鼠的治疗作用

陈慧1,李亨1,岳龙涛2,张民1,王聪聪1,王杉1,张蓬1,段瑞生1   

  1. 山东大学附属千佛山医院 1.神经内科;2.中心实验室, 山东 济南 250014
  • 收稿日期:2015-08-21 出版日期:2016-04-10 发布日期:2016-04-10
  • 通讯作者: 段瑞生. E-mail: ruisheng_duan@yahoo.com E-mail:ruisheng_duan@yahoo.com
  • 基金资助:
    山东省泰山学者建设工程专项经费(20130914);国家自然科学基金(81471222)

Therapeutic effects of AG490 on experimental autoimmune myasthenia gravis in Lewis rats

CHEN Hui1, LI Heng1, YUE Longtao2, ZHANG Min1, WANG Congcong1, WANG Shan1, ZHANG Peng1, DUAN Ruisheng1   

  1. 1. Department of Neurology;
    2.Central Laboratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China
  • Received:2015-08-21 Online:2016-04-10 Published:2016-04-10

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摘要： 目的 探讨JAK2/STAT3通路抑制剂AG490对实验性自身免疫性重症肌无力(EAMG)大鼠的治疗作用。 方法 用人工合成的大鼠乙酰胆碱受体α亚基的97-116肽段免疫Lewis大鼠,建立EAMG模型,将12只大鼠随机、平均分为AG490治疗组及对照组,双盲法隔日评估大鼠临床症状并评分。流式细胞术检测淋巴结单个核细胞中细胞因子IL-6及IL-21的分泌;CCK-8及羟基荧光素琥珀酰亚胺酯(CFSE)检测淋巴结单个核细胞的增殖;ELISA检测大鼠血清中抗R97-116抗体水平。 结果 自免疫后第13天开始,AG490治疗组临床症状较对照组明显缓解,并且第27、29、31、33、37、39、41天时,两组肌力评分的差异有统计学意义(P<0.05);与对照组相比,AG490治疗组中的细胞因子IL-6、IL-21的分泌减少(P<0.01);AG490治疗组中抗R97-116抗体IgG、IgG2b的分泌减少(P<0.01);与对照组相比,AG490治疗组的淋巴细胞的增殖受到抑制。 结论 AG490通过抑制细胞因子IL-6及IL-21的分泌,降低大鼠血清中抗R97-116抗体IgG、IgG2b水平,缓解EAMG大鼠病情。

关键词: 实验性自身免疫性重症肌无力, AG490, IL-6, IL-21, 抗R97-116抗体

Abstract: Objective To investigate the effect of AG490 on Lewis rats with experimental autoimmune myasthenia gravis(EAMG). Methods The EAMG model was established by immunization of Lewis rats with R97-116 peptide. Twelve rats were randomly divided into two groups(n=6 in each group), i.e, the control group and the AG490 treatment group. The levels of intracellular IL-6 and IL-21 were analyzed by flow cytometry. The lymphocyte proliferation was determined by CCK-8 and CFSE. Anti-R97-116 IgG and subtypes in the serum were detected by ELISA. Results From day 13 after immunization, the clinical symptoms of the AG490 group were obviously ameliorated, especially on day 27, 29, 31, 33, 37, 39 and 41(P<0.05), compared with the control group. Besides this, the AG490 treatment group also showed decreased secretion of IL-6 and IL-21(P<0.01), reduced anti-R97-116 peptide IgG and IgG2b(P<0.01), and suppressed lymphocyte(in particular CD4+ T cells)proliferation, compared with the control group. Conclusion AG490 can ameliorate EAMG by down-regulating the secretion of IL-6 and IL-21, which further reduces anti-R97-116 peptide IgG and IgG2b.

Key words: Anti-R97-116 antibody, AG490, IL-21, Experimental autoimmune myasthenia gravis, IL-6

中图分类号: 

  • R746.1
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