应用AG490阻断STAT3对系统性红斑狼疮Th17/Treg平衡的调控研究  

Application of AG490 to Regulation Th17/Treg Balance in Systemic Lupus Erythematosus by Blocking STAT3

作　　者：黄可可[1] 周春燕 颜志婷 叶海燕 HUANG Keke;ZHOU Chunyan;YAN Zhiting;YE Haiyan(Pingxiang People’s Hospital,Pingxiang 337000,China)

机构地区：[1]江西省萍乡市人民医院

出　　处：《中国医学创新》2019年第34期141-145,共5页Medical Innovation of China

基　　金：江西省卫生计生委科技计划项目(20174030)

摘　　要：目的:研究应用免疫抑制剂AG490阻断信号传导与转录活化因子3(STAT3)对系统性红斑狼疮(SLE)患者辅助性T细胞17(Th17)/调节性T细胞(Treg)平衡的调控。方法:选取本院于2018年10月-2019年6月收治的10例SLE(观察组)以及10例体检健康者(对照组),抽取所有受试者外周血约10 mL,采用免疫磁珠法提取CD4^+T细胞,并用流式细胞术检测所有受试者Th17/Treg细胞亚群变化。用AG490(0、25、50、100μM)处理患者CD4^+T细胞,检测Th17/Treg细胞亚群以及细胞因子变化,并采用Q-PCR了解STAT3、Foxp3、RORγt水平。结果:观察组患者Th17显著高于对照组,而Treg水平显著低于对照组,两组患者Th17/Treg比较,差异有统计学意义(P<0.05)。随着AG490浓度的增加,Th17/Treg比值、IL-6、IL-17表达水平均逐渐降低,而IL-10、TGF-β水平均显著增加,各组间比较差异均有统计学意义(P<0.05)。经过不同浓度AG490处理后,STAT3、RORγt mRNA水平以及STAT3蛋白水平均显著降低,其中100μM剂量组蛋白水平显著低于其他三组,而Foxp3 mRNA水平显著增加,各组mRNA水平比较,差异均有统计学意义(P<0.05)。结论:通过阻断STAT3信号通路,可诱导Treg分化以及抑制Th17分化,从而调控Th17/Treg平衡,可为系统性红斑狼疮的治疗提供新方向。Objective: To study the regulation of Th17/Treg balance in systemic lupus erythematosus by blocking STAT3. Method: A total of 10 cases of SLE(observation group) and 10 healthy persons undergoing physical examination(control group) were selected in our hospital from October 2018 to June 2019. All subjects were drawn with peripheral blood of about 10 mL, CD4^+ T cells were extracted by immunomagnetic beads method and the changes of Th17/Treg cell subsets were detected by flow cytometry. CD4^+ T cells were treated with AG490(0, 25, 50, 100 μM), the changes of Th17/Treg cell subsets and cytokines were detected and the levels of STAT3, Foxp3, RORγt were detected by Q-PCR. Result: The level of Th17 in the observation group was significantly higher than that in the control group, but the level of Treg was significantly lower than that in the control group, there was significant difference in Th17/Treg between the two groups(P<0.05). With the increase of AG490 concentration, the expression level of Th17/Treg ratio and IL-6, IL-17 decreased gradually, while the level of IL-10, TGF-β increased significantly, with significant difference among the groups(P<0.05). After AG490 treatment, the levels of STAT3, RORγt mRNA and STAT3 protein were significantly decreased, the levels of 100 μM dose group were significantly lower than those of the other three groups, while the level of Foxp3 mRNA was significantly increased, and the level of mRNA in each group was significantly different(P<0.05). Conclusion: Blocking STAT3 signaling pathway can induce Treg differentiation and inhibit Th17 differentiation, thus regulating Th17/Treg balance, which can provide a new direction for the treatment of systemic lupus erythematosus.

关 键 词：信号传导与转录活化因子 3系统性红斑狼疮 辅助性T细胞17 调节性T细胞 

分 类 号：R593.241[医药卫生—内科学]