Hu Jinyang, Niu Junjie, Jiang Shisheng, Wu Yuhua
Department of Spleen, Gastroenterology and Hepatology, Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Changsha, China.
Department of Radiation Oncology, Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Changsha, China.
J Innate Immun. 2025;17(1):262-276. doi: 10.1159/000545394. Epub 2025 May 14.
Qilian Jiechang Ning (QJN), a traditional Chinese herbal formula, has demonstrated potential therapeutic effects in the treatment of ulcerative colitis (UC). This study aims to investigate the mechanism of QJN in the outer membrane vesicles (OMVs) of Segatella copri (S. copri)-induced colon epithelial cells and UC mice.
Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were utilized to assess the morphology and size of OMVs. Inflammation markers and tight junction protein levels in HCoEpiCs induced by OMVs were monitored using ELISA and western blot. QJN was administered to intervene in HCoEpiCs treated with S. copri OMVs. Additionally, trinitrobenzene sulfonic acid (TNBS)-induced mouse models were conducted to evaluate the therapeutic effects of QJN on UC.
S. copri OMVs treated with QJN demonstrated a significant reduction in particle size, protein concentration, and LPS content. In HCoEpiCs, QJN effectively decreased the expression of inflammation-inducing cytokines (IL-1β, IL-18, IL-6, TNF-α) and proinflammatory proteins (GSDMD-N, NLRP3, ASC, cleaved Caspase-1, cleaved Caspase-4) triggered by S. copri OMVs, while enhancing the expression of tight junction proteins (ZO-1 and Occludin). In the UC mouse models, QJN significantly reduced the Disease Activity Index (DAI), improved colon length, lowered LPS levels, ameliorated colonic tissue damage, and inhibited Caspase-1- and Caspase-11-dependent inflammatory responses.
QJN can alleviate S. copri-OMV-induced inflammatory response in colonic epithelial cells and reduce symptoms of UC in mouse models by modulating the Caspase-1 and Caspase-11 pathways.
中药复方芪连结肠宁（QJN）在溃疡性结肠炎（UC）的治疗中已显示出潜在的治疗效果。本研究旨在探讨芪连结肠宁对由普通拟杆菌（S. copri）外膜囊泡（OMVs）诱导的结肠上皮细胞和UC小鼠的作用机制。
采用透射电子显微镜（TEM）和纳米颗粒跟踪分析（NTA）评估OMVs的形态和大小。使用酶联免疫吸附测定（ELISA）和蛋白质免疫印迹法监测由OMVs诱导的人结肠上皮细胞（HCoEpiCs）中的炎症标志物和紧密连接蛋白水平。给予芪连结肠宁干预经普通拟杆菌OMVs处理的HCoEpiCs。此外，构建三硝基苯磺酸（TNBS）诱导的小鼠模型以评估芪连结肠宁对UC的治疗效果。
经芪连结肠宁处理的普通拟杆菌OMVs的粒径、蛋白质浓度和脂多糖（LPS）含量显著降低。在HCoEpiCs中，芪连结肠宁有效降低了由普通拟杆菌OMVs触发的炎症诱导细胞因子（IL-1β、IL-18、IL-6、TNF-α）和促炎蛋白（Gasdermin D-N端、NLRP3、凋亡相关斑点样蛋白（ASC）、裂解的半胱天冬酶-1、裂解的半胱天冬酶-4）的表达，同时增强了紧密连接蛋白（紧密连接蛋白1（ZO-1）和闭合蛋白）的表达。在UC小鼠模型中，芪连结肠宁显著降低疾病活动指数（DAI），改善结肠长度，降低LPS水平，减轻结肠组织损伤，并抑制半胱天冬酶-1和半胱天冬酶-11依赖性炎症反应。
芪连结肠宁可通过调节半胱天冬酶-1和半胱天冬酶-11途径减轻普通拟杆菌OMV诱导的结肠上皮细胞炎症反应，并减轻小鼠模型中的UC症状。
