首页|基于IL-6/STAT3信号通路探讨电针对溃疡性结肠炎小鼠Th17/Treg免疫平衡的影响

基于IL-6/STAT3信号通路探讨电针对溃疡性结肠炎小鼠Th17/Treg免疫平衡的影响

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目的 观察电针通过调控白细胞介素-6(IL-6)/信号转导与转录活化因子3(STAT3)信号通路,影响葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)小鼠辅助性T细胞17(Th17)/调节性T细胞(Treg)之间的免疫平衡,探讨电针治疗UC的部分机制。方法 雄性C57BL/6N小鼠采用DSS自由饮水法建立UC模型后,随机分为模型组、电针组和假针组,每组10只,另取10只作为空白对照组。选取双侧"天枢""上巨虚"进行电针或假针治疗,每次20 min,共10次。观察各组小鼠的一般情况、疾病活动指数(DAI),HE染色法观察结肠组织病理学变化,ELISA法检测血清中IL-6、IL-10和IL-17含量,Western blot法检测结肠组织中IL-6、STAT3、维甲酸相关孤儿受体(RORγt)和叉头框蛋白P3(FoxP3)的蛋白表达水平,流式细胞术检测小鼠脾脏中Th17和Treg细胞的占比。结果 与空白组相比,模型组小鼠DAI评分明显升高(P<0。01),出现结肠黏膜破损、大量炎性细胞浸润等表现,血清IL-6、IL-17含量明显增加(P<0。01)、IL-10含量明显减少(P<0。01),结肠组织中IL-6、STAT3和RORγt的表达均明显增加(P<0。01),FoxP3的表达降低(P<0。05),脾脏中Th17细胞百分比升高、Treg细胞百分比降低(P<0。05)。与模型组相比,电针组小鼠DAI评分降低(P<0。05),结肠损伤减轻,炎性浸润减少,血清IL-6、IL-17含量减少、IL-10含量增加(P<0。05),结肠组织中IL-6、STAT3、RORγt表达均明显降低(P<0。01)、FoxP3表达增加(P<0。05),脾脏中Th17细胞百分比下降、Treg细胞百分比升高(P<0。05)。而假针组小鼠结肠损伤未见好转,与模型组相比,各指标变化未见统计学差异。结论 电针可能通过下调IL-6/STAT3信号通路,促进Th17/Treg恢复免疫平衡,从而改善UC小鼠的肠道炎症,发挥治疗UC的作用效应。
Exploring the Effect of Electroacupuncture on Th17/Treg Immune Balance in Mice with Ulcerative Colitis Based on IL-6/STAT3 Signaling Pathway
Objective To observe the effect of electroacupuncture(EA)on the immune balance between helper T cell 17(Th 17)/regulatory T cells(Treg)in the spleens of mice with dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)by modulating the interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3)signaling pathway,and to explore part of the mechanism of EA on treating UC.Methods Male C57BL/6N mice were randomly divided into UC model group,EA group,and sham acupuncture(SA)group,with 10 mice in each group,and 10 mice in the blank control group.After establishing the UC model mice by DSS free-drinking method,bilateral"Tianshu(ST25)"and"Shangjiuxu(ST37)"were selected for EA or SA treatment for 20 min each time,with a total of 10 times.The general condition and disease activity index(DAI)of the mice in each group were observed,the pathological changes of colon tissue were observed by HE staining,the levels of IL-6,IL-10 and IL-17 in serum were detected by ELISA,and the protein expression levels of IL-6,STAT3,retinoic acid-related orphan receptor gamma t(RORγt)and Forkhead box protein P3(FoxP3)were detected by Western blot in the colon tissue.Results Compared with the blank group,mice in the model group had significantly higher DAI scores(P<0.01),with colonic mucosal rupture and massive inflammatory cell infiltration.Significant increases were detected in serum IL-6 and IL-17 levels(P<0.01),with significant reductions in IL-10 levels(P<0.01).Significant increases were detected in the expression of IL-6,STAT3,and RORγt in colonic tissues(P<0.01),with the decreased expression of FoxP3(P<0.05).The percentage of Th17 cells in the spleen was increased and the percentage of Treg cells was decreased(P<0.05).Compared with the model group,mice in the EA group had lower DAI scores(P<0.05),with reduced colonic injury,decreased inflammatory infiltration.Decreased serum IL-6 and IL-17 levels,with increased IL-10 levels(P<0.05)were detected.Significantly lower IL-6,STAT3,and RORγt expression in the colonic tissues(P<0.01),and increased FoxP3 expression(P<0.05)were detected,as well as the decreased percentage of Th17 cells and increased percentage of Treg cells in spleen(P<0.05).However,the colonic injury of mice in the SA group did not show any improvement,and no statistical difference was observed in these indexes compared with the model group.Conclusion EA may exert a therapeutic effect on UC by down-regulating the IL-6/STAT3 signaling pathway and promoting the restoration of immune balance by Th17/Treg,thereby diminishing intestinal inflammation in UC mice.

ElectroacupunctureUlcerative colitisIL-6STAT3Th17 cellTreg cell

殷萱、郭修田、崔凯宇、曾晓铃、徐世芬

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上海中医药大学附属市中医医院 上海 200071

电针 溃疡性结肠炎 白细胞介素-6 信号转导与转录活化因子3 辅助性T细胞 调节性T细胞

2024

世界科学技术-中医药现代化
中科院科技政策与管理科学研究所,中国高技术产业发展促进会

世界科学技术-中医药现代化

CSTPCD北大核心
影响因子:1.175
ISSN:1674-3849
年,卷(期):2024.26(11)