白术内酯Ⅲ在小鼠慢性炎性肠病模型中通过抑制STAT3信号维持Th17/Treg平衡  

AtractylenolideⅢmaintains Th17/Treg balance by inhibiting STAT3 signaling in a mouse model of chronic inflammatory bowel disease

作　　者：方瑞康 张冬娜 李菁菁 朱羿龙[1] 张海洋[1] 高旭[2] 朱光泽[1,3] 李一权 韩继成[1] FANG Ruikang;ZHANG Dongna;LI Jingjing;ZHU Yilong;ZHANG Haiyang;GAO Xu;ZHU Guangze;LI Yiquan;HAN Jicheng(Key Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases,College of Integrative Medicine,Changchun University of Chinese Medicine,Changchun 130117,China;College of Agriculture,Yanbian University,Yanbian 133000,China;Clinical Laboratory,Affiliated Hospital of Changchun University of Traditional Chinese Medicine,Changchun 130021,China)

机构地区：[1]长春中医药大学中西医结合学院吉林省传染性疾病中医药防治重点实验室,吉林长春130117 [2]延边大学农学院,吉林延边133000 [3]长春中医药大学附属医院检验科,吉林长春130021

出　　处：《中国病理生理杂志》2024年第12期2336-2342,共7页Chinese Journal of Pathophysiology

基　　金：吉林省自然科学基金项目(No.YDZJ202201ZYTS254)。

摘　　要：目的:探究白术内酯Ⅲ(AⅢ)对葡聚糖硫酸钠(DSS)诱导的小鼠慢性炎性肠病(IBD)模型损伤的作用,及其调控信号转导及转录激活因子3(STAT3)信号干预Th17/Treg平衡的作用机制。方法:40只SPF级雌性C57BL/6小鼠随机分为对照组、模型组、高剂量(50 mg/kg)AⅢ治疗组和低剂量(30 mg/kg)AⅢ治疗组,每组10只。模型组和治疗组基于3%DSS溶液建立慢性IBD小鼠模型,对照组给予正常饮用水。通过疾病活动度指数(DAI)分析小鼠疾病活动程度;HE染色观察慢性IBD小鼠结肠组织病理学损伤情况;通过免疫组化及Western blot分析各组小鼠结肠组织中磷酸化STAT3及紧密连接相关蛋白[闭合蛋白(occludin)和闭锁小带蛋白1(ZO-1)]水平;通过流式细胞术分析小鼠脾脏淋巴细胞Th17和Treg的分化能力。结果:DAI和HE染色结果显示,AⅢ可有效减轻DSS诱导的慢性IBD小鼠炎症损伤(P<0.01)。免疫组化结果显示,AⅢ可增加结肠组织中ZO-1和occludin蛋白的表达量(P<0.01)。流式细胞术结果显示,AⅢ可调节脾脏中Th17/Treg的比值并维持其平衡(P<0.01)。免疫组化和Western blot结果显示,AⅢ可抑制STAT3蛋白的磷酸化(P<0.01)。结论:AⅢ可能通过抑制STAT3磷酸化维持Th17/Treg平衡,从而减轻慢性IBD小鼠的炎症损伤。AIM:To investigate the potential of atractylenolideⅢ(AⅢ)in mitigating dextran sulfate sodium(DSS)-induced injury in a mouse model of chronic inflammatory bowel disease(IBD),and to explore the mechanisms involved,particularly the modulation of signal transducer and activator of transcription 3(STAT3)signaling,which plays a crucial role in the homeostasis of T helper 17(Th17)and regulatory T(Treg)cells.METHODS:A mouse model of DSSinduced chronic IBD was established,and the mice were divided into 4 groups:control,model(DSS),high-dose(50 mg/kg)AⅢ,and low-dose(30 mg/kg)AⅢ.The disease activity index(DAI)was utilized to assess disease severity.Histopathological damage in the colons of IBD mice was evaluated by hematoxylin-eosin(HE)staining.The protein levels of phosphorylated STAT3,occludin and zonula occludens-1(ZO-1)were analyzed using immunohistochemical staining and Western blot.Flow cytometry was employed to examine the differentiation of splenic lymphocytes into Th17/Treg cells. RESULTS: Both DAI assessments and HE staining indicated that AⅢ significantly alleviated inflammatory injury in mice with DSS-induced chronic IBD. Immunohistochemical analysis demonstrated that AⅢ enhanced the expression of ZO-1 and occludin in colonic tissues. Flow cytometry results revealed that AⅢ helped maintain the balance between splenic Th17 and Treg cells. Furthermore, immunohistochemical staining and Western blot showed that AⅢ inhibited the phos-phorylation of STAT3. CONCLUSION: Treatment with AⅢ effectively reduced inflammatory injury in a mouse model of chronic IBD by preserving Th17/Treg homeostasis through the inhibition of STAT3 phosphorylation. As a natural com-pound, AⅢ exhibits significant therapeutic potential for the treatment of chronic IBD.

关 键 词：白术内酯Ⅲ 炎性肠病 Th17/Treg平衡 STAT3信号通路 

分 类 号：R285.5[医药卫生—中药学] R574.62[医药卫生—中医学] R363