鼠乳杆菌通过抑制IL-17分泌缓解DSS诱导的小鼠结肠炎  

Lactobacillus murinus alleviates DSS-induced colitis in mice by inhibiting IL-17 secretion

作　　者：李建洪 徐婧 郭雪 胡金霞 徐豪明 周有连 聂玉强[1,2] LI Jianhong;XU Jing;GUO Xue;HU Jinxia;XU Haoming;ZHOU Youlian;NIE Yuqiang(Department of Gastroenterology and Hepatology,the Second Affiliated Hospital,School of Medicine,South China University of Technology,Guangzhou,Guangdong,China;Department of Gastroenterology and Hepatology,Guangzhou First People′s Hospital,South China University of Technology,Guangzhou,Guangdong,China)

机构地区：[1]华南理工大学医学院第二附属医院消化内科,510180 [2]广州市第一人民医院消化内科,510180

出　　处：《现代消化及介入诊疗》2024年第10期1180-1185,1192,共7页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：国家自然科学基金(82370552、82270577、82470579);广东省自然科学基金(2023A1515030214)。

摘　　要：目的探讨鼠乳杆菌(Lactobacillus murinus,L.m)对葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的小鼠结肠炎炎症的缓解作用以及作用机制。方法将6~8周龄无特定病原体级(specific pathogen free,SPF)的雄性C57BL/6小鼠随机分为3组,分别是:正常对照(Control)组、DSS组和Lactobacillus murinus(L.m+DSS)组,每组6只。对照组小鼠自由饮水,其余两组小鼠饮用水中添加3%(w/w)DSS,自由饮用7天。所培养出的Lactobacillus murinus调整浓度为1×10^(8)CFU,在DSS造模期间于干预组连续灌胃干预7天,灌胃量200μL/只;DSS组用等量磷酸缓冲盐溶液(phosphate buffer saline,PBS)溶液灌胃。每日观察记录小鼠体质量下降程度、腹泻程度及血便情况,并评估其疾病活动指数(disease activity index,DAI)。于实验终点观察小鼠结肠并测量长度,对各组小鼠的结肠组织病理学进行评分。采用qPCR检测各组小鼠肠道屏障和炎症因子mRNA相对表达水平变化;通过流式细胞术检测各组肠辅助性T细胞(helper T cell,Th17)占单核细胞比例。结果Lactobacillus murinus可改善DSS诱导的小鼠结肠炎症状,如体重减轻、腹泻血便、结肠长度缩短以及结肠病理损伤;并降低促炎细胞因子IL-6、IL-1β和TNF-α等的表达,增加保护性屏障因子ZO-1、MUC-2、Occludin和E-Cadherin表达;并可减少CD4^(+)T细胞中Th17细胞比例。结论鼠乳杆菌可改善结肠炎小鼠炎症及肠屏障损伤,其机制可能为抑制肠道Th17细胞的生成,减少结肠组织炎性细胞因子IL-17A分泌。Objective To investigate the alleviating effect and mechanism of Lactobacillus murinus(L.murinus)on dextran sodium sulfate(DSS)-induced colitis in mice.Methods Male C57BL/6 mice aged 6-8 weeks with specific pathogen free(SPF)were randomly divided into three groups:normal control group,DSS group,and L.murinus(L.m+DSS)group,with six mice in each group.The mice in the control group were allowed to drink water freely,while the mice in the other two groups were given 3%(w/w)DSS in their drinking water and allowed to drink freely for 7 days.The concentration of the cultured L.murinus was adjusted to 1×10^(8)CFU,and during the DSS modeling period,the intervention group was continuously administered 200ul/mouse of the intervention solution for 7 days;the DSS group was given an equal amount of phosphate buffer saline(PBS)solution by gavage.The daily observation records of the mice′s body mass loss,diarrhea severity,and bloody stool conditions were recorded,and their disease activity index(DAI)was evaluated.At the end of the experiment,the colons of mice were observed and measured for length,and the histopathology of the colonic tissue of each group of mice was scored.The relative expression levels of the intestinal barrier and inflammatory factor mRNA in each group of mice were detected by qPCR;The proportion of helper T cells(Th17)in each group was detected by flow cytometry.Results L.murinus can improve the symptoms of DSS-induced colitis in mice,such as weight loss,diarrhea with bloody stool,shortened colon length,and pathological damage to the colon;It also reduces the expression of pro-inflammatory cytokines such as IL-6,IL-1β,and TNF-α,and increases the expression of protective barrier factors such as ZO-1,MUC-2,Occludin,and E-Cadherin;and can reduce the proportion of Th17 cells in CD4^(+)T cells.Conclusion L.murinus can improve inflammation and intestinal barrier injury in colitis mice,and its mechanism may be related to the inhibition of the production of Th17 cells in the intestine and the reduction of the s

关 键 词：鼠乳杆菌 溃疡性结肠炎 TH17细胞 炎症 

分 类 号：R574[医药卫生—消化系统]