AG490对实验性自身免疫性重症肌无力大鼠的治疗作用

Therapeutic effects of AG490 on experimental autoimmune myasthenia gravis in Lew is rats

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Ig G、Ig G2b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Ig G、Ig G2b水平,缓解EAM G大鼠病情。

Objective To investigate the effect of AG490 on Lew is rats w ith experimental autoimmune myasthenia gravis（ EAM G）. Methods The EAM G model w as established by immunization of Lew is rats w ith R97-116 peptide.Tw elve rats w ere randomly divided into tw o 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 w ere analyzed by flow cytometry. The lymphocyte proliferation w as determined by CCK-8 and CFSE. Anti-R97-116 Ig G and subtypes in the serum w ere detected by ELISA. Results From day 13 after immunization,the clinical symptoms of the AG490 group w ere obviously ameliorated,especially on day 27,29,31,33,37,39 and 41（ P〈0. 05）,compared w ith the control group. Besides this,the AG490 treatment group also show ed decreased secretion of IL-6 and IL-21（ P〈0. 01）,reduced anti-R97-116 peptide Ig G and Ig G2b（ P〈0. 01）,and suppressed lymphocyte（ in particular CD4^＋T cells） proliferation,compared w ith the control group.Conclusion AG490 can ameliorate EAM G by dow n-regulating the secretion of IL-6 and IL-21,w hich further reduces anti-R97-116 peptide Ig G and Ig G2 b.