4'-羟基查尔酮通过调节Th17/Treg平衡治疗溃疡性结肠炎  

4'-Hydroxychalcone attenuates ulcerative colitis by regulating Th17/Treg homeostasis

作　　者：刘芸芸 张冬娜 李善智 朱羿龙[1] 方瑞康 朱光泽[2] 李一权 宗宇平 韩继成[1] LIU Yunyun;ZHANG Dongna;LI Shanzhi;ZHU Yilong;FANG Ruikang;ZHUGuangze;LI Yiquan;ZONG Yuping;HAN Jicheng(College of Integrative Medicine,Changchun University of Chinese Medicine,Changchun 130117,China;Department of Clinical Laboratory,Affiliated Hospital of Changchun University of Chinese Medicine,Changchun 130117,China;School of Medical Inspection,Jilin Medical University,Chuangchun 132013,China;Staff Ward,Hospital 964,Joint Logistic Support Force,Changchun 130000,China)

机构地区：[1]长春中医药大学中西医结合学院,吉林长春130117 [2]长春中医药大学附属医院检验科,吉林长春130117 [3]吉林医药学院检验学院,吉林长春132013 [4]联勤保障部队第964医院干部病房,吉林长春130000

出　　处：《中国病理生理杂志》2025年第1期81-89,共9页Chinese Journal of Pathophysiology

基　　金：吉林省自然科学基金资助项目(No.YDZJ202201ZYTS257,No.YDZJ202201ZYTS254);吉林省科技发展计划项目(No.20220508075RC)。

摘　　要：目的:从调节Th17/Treg平衡途径阐述4'-羟基查尔酮(4-HC)对结肠炎小鼠的干预以及作用机制。方法:基于葡聚糖硫酸钠(DSS)的小鼠结肠炎疾病模型,通过HE染色等对结肠组织的病理学特点进行了细致观察;同时,采用免疫组化分析及Western blot技术,检测了JAK/STAT信号通路相关蛋白以及紧密连接蛋白(ZO-1和occludin)的表达水平。流式细胞术分析Th17/Treg细胞分化情况。结果:DSS诱导小鼠体重减轻,腹泻,便血,DAI积分明显增加,结肠长度明显缩短。4-HC治疗组小鼠体重初步下降后,呈现恢复趋势,腹泻及便血症状有所改善,与模型组比较,DAI评分明显下降,结肠长度增加。4-HC能明显改善肠道黏膜屏障功能、增加肠道内杯状细胞的数目以及小鼠的肠道隐窝结构。Wester blot结果显示,与模型组相比,4-HC处理后,ZO-1和occludin在结肠组织中的表达明显升高。用流式细胞仪检测T细胞分化情况,发现相较于模型组,小鼠脾淋巴细胞和肠系膜淋巴结中Th17分化率明显下降,而Treg细胞分化率明显上升。免疫组织化学及Western blot实验进一步验证了4-HC对STAT1和STAT3磷酸化水平的显著抑制作用,并上调了STAT6的磷酸化水平,提示4-HC可能通过调控JAK-STAT信号通路调控CD4+T细胞功能。结论:4-HC延缓DSS诱导的结肠炎小鼠的病情进展、改善结肠组织损伤,调节Th17/Treg平衡可能与JAK/STAT信号通路有关。AIM:To elucidate the intervention and mechanism of 4'-hydroxychalcone(4-HC)in colitis mice through the regulation of Th17/Treg homeostasis.METHODS:Using a dextran sodium sulfate(DSS)-induced colitis model in mice,we meticulously observed the pathological characteristics of colon tissue via HE staining.Additionally,we employed immunohistochemical analysis and Western blot techniques to assess the expression levels of proteins associated with the JAK/STAT signaling pathway,as well as the specific content of tight junction proteins such as ZO-1 and occludin.The differentiation of Th17 and Treg cells was analyzed through flow cytometry.RESULTS:Compared to the normal group,the DSS group exhibited a consistent decline in body weight,coupled with symptoms of diarrhea and hematochezia,an increase in the DAI score,and a notable reduction in colon length.In contrast,the body weight of the 4-HC group dis played an upward trend following an initial decrease,with improvements in diarrhea and hematochezia symptoms,a reduction in the DAI score,and a restoration of colon length relative to the model group.The integrity of colon tissue in the 4-HC group was significantly better than that in the DSS group,evidenced by a marked increase in the number of goblet cells and an enhancement in crypt integrity,while the average histology score showed a decrease.Western blot analysis revealed substantial increase in ZO-1 and occludin expression after 4-HC treatment.Flow cytometry results indicated a dramatic decrease in the differentiation rate of Th17 cells in spleen lymphocytes and mesenteric lymph nodes,while the differentiation rate of Treg cells was significantly elevated.Immunohistochemical and Western blot analyses demonstrated that 4-HC markedly reduced the phosphorylation of STAT1 and STAT3,while up-regulating the phosphorylation of STAT6,suggesting that 4-HC modulates CD4+T cell activity through the JAK-STAT pathway.CONCLUSION:The 4-HC may enhance the course of DSS-induced colitis in mice,alleviate colonic tissue damage,and modul

关 键 词：4'-羟基查尔酮 溃疡性结肠炎 Th17/Treg体内平衡 JAK/STAT信号通路 

分 类 号：R574.62[医药卫生—消化系统] R965[医药卫生—内科学] R363[医药卫生—临床医学]