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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 therapeutic effect of JAK2 / STAT3 pathway inhibitor AG490 on experimental autoimmune myasthenia gravis (EAMG) in rats. Methods The Lewis rats were immunized with the 97-116 peptide of the α subunit of the rat acetylcholine receptor and the EAMG model was established. Twelve rats were randomly divided into AG490 treatment group and control group, Rats clinical symptoms and score. Flow cytometry was used to detect the secretion of cytokines IL-6 and IL-21 in lymph node mononuclear cells. Proliferation of lymphonuclear mononuclear cells was detected by CCK-8 and hydroxy fluorescein succinimidyl ester (CFSE) Anti-R97-116 antibody levels. Results From the 13th day after immunization, the clinical symptoms of AG490 group were significantly relieved compared with the control group, and there was significant difference between the two groups on the 27th, 29th, 31st, 33th, 37th, 39th and 41st days (P <0.05). Compared with the control group, the secretion of cytokines IL-6 and IL-21 in AG490 treatment group decreased (P <0.01); the secretion of anti-R97-116 IgG and Ig G2b in AG490 treatment group decreased (P <0.01). Compared with the control group, the proliferation of lymphocytes in AG490-treated group was inhibited. Conclusion AG490 can relieve the EAM G rats by inhibiting the secretion of cytokines IL-6 and IL-21 and decreasing the level of Ig G and Ig G2b of anti-R97-116 in serum of rats.