摘要
目的探讨Toll样受体4(TLR4)及其下游核因子κB(NF-κB)及p38丝裂原活化蛋白激酶(p38 MAPK)/CJun氨基末端激酶(JNK)信号通路在普拉梭菌对实验性溃疡性结肠炎(UC)小鼠肠道的保护作用。方法30只C57BL/6小鼠分为正常对照组、模型组、普拉梭菌组。模型组、普拉梭菌组饮用3%葡聚糖硫酸钠(DSS)溶液建立UC模型;同时,普拉梭菌组给予0.2 mL/10 g普拉梭菌的菌液灌胃干预,正常对照组和模型组给予0.2 mL/kg生理盐水灌胃。干预7 d后,比较各组疾病活动指数(DAI)和组织学损伤指数(HI)评分,RT-PCR检测TLR4、NF-κB、p38MAPK、JNK mRNA表达,ELISA法检测小鼠结肠白细胞介素-17(IL-17)、IL-6、肿瘤坏死因子-α(TNF-α)、IL-10及血清中二胺氧化酶(DAO)、D-乳酸(D-Lac)表达,比较各组小鼠肠黏膜屏障、肠道菌群的差异。结果与对照组比较,模型组结肠中TLR4、NF-κB、p38 MAPK、JNK的mRNA表达增高,结肠中IL-17、TNF-α、IL-6表达量增高,IL-10表达降低,血清中DAO及D-Lac水平增高,粪便中双歧杆菌、乳酸杆菌数目减少,肠杆菌、肠球菌数目增加,差异均有统计学意义(P均<0.05);与模型组比较,普拉梭菌组结肠中TLR4、NF-κB、p38 MAPK、JNK的m RNA表达降低,结肠IL-17、TN F-a、IL-6表达量降低,IL-10表达增高,血清中DAO及D-Lac水平降低,粪便中双歧杆菌、乳酸杆菌数目增加,肠杆菌、肠球菌数目减少,差异均有统计学意义(P均<0.05)。结论普拉梭菌能够对3%DSS诱导的小鼠UC模型起到保护作用,其作用机制可能与抑制TLR4及其下游NF-κB、p38 MAPK/JNK信号通路有关。
Objective To investigate the role of Toll-like receptor 4(TLR4)and its downstream nuclear factor-κB(NF-κB)and p38 mitogen-activated protein kinases(MAPK)/c-Jun N-terminal kinase(JNK)signaling pathways in intestinal protection of Faecalibacterium prausnitzii against experimental ulcerative colitis(UC).Methods Thirty C57BL/6 mice were assigned to three groups:normal control group,model group and Faecalibacterium prausnitzii group.Mice in model group and Faecalibacterium prausnitzii group drank 3%dextran sulfate sodium salt(DSS)solution to establish UC model,at the same time,mice in Faecalibacterium prausnitzii group was given 0.2 m L/10 g Faecalibacterium prausnitzii solution by intragastric intervention,and mice in normal control group and model group were given 0.2 m L/kg normal saline by intragastric intervention.After 7 days of intervention,disease activity index(DAI)and histological injury index(HI)scores were compared,the mRNA levels of TLR4,NF-κB,p38 MAPK and JNK were detected by RT-PCR,the levels of interleukin-17(IL-17),IL-6,tumor necrosis factor-α(TNF-α),IL-10 in colon and the diamine oxidase(DAO)and D-lactate(D-Lac)in serum were detected by ELISA,and the intestinal mucosal barrier and intestinal flora were compared in each group.Results Compared with the control group,the mRNA expressions of TLR4,NF-κB,p38 MAPK and JNK in colon were increased;the expression levels of IL-17,TNF-αand IL-6 in colon were increased;the expression level of IL-10 was decreased;the levels of DAO and D-LAC in serum were increased,and the number of Bifidobacteria and Lactobacillus in feces were significantly decreased;the number of Enterobacter and Enterococcus increased in model group(all P<0.05).Compared with the model group,the mRNA expression levels of TLR4,NF-κB,p38 MAPK and JNK in colon were decreased,the expression levels of IL-17,TNF-αand IL-6 in colon were decreased,the expression level of IL-10 was increased,the levels of DAO and D-LAC in serum were decreased,and the number of Bifidobacterium and Lactobacillus in feces were increased,and the number of Enterobacteria and Enterococcus decreased in Faecalibacterium prausnitzii group(all P<0.05).Conclusion Faecalibacterium prausnitzii could protect the mouse UC model induced by 3%DSS,and the mechanism might be related to the inhibition of TLR4 and its downstream NF-κB and p38 MAPK/JNK signaling pathways.
作者
赵翠娟
段聿
陈强
ZHAO Cui⁃juan;DUAN Yu;CHEN Qiang(Department of Gastrorenterology,the Third Affiliated Hospital of Inner Mongolia Medical University(Inner Mongolia Baogang Hospital)Baotou,Inner Mongolia 014010;Department of Burns,the Third Affiliated Hospital of Inner Mongolia Medical University(Inner Mongolia Baogang Hospital),Burn Research Institute of Inner Mongolia,Baotou,Inner Mongolia 014010,China)
出处
《热带医学杂志》
CAS
2022年第6期763-767,817,895,共7页
Journal of Tropical Medicine
基金
内蒙古自治区自然科学基金项目(2020MS08024)
包头市科技计划项目(2018C2007-3-15)
中国金属学会冶金安全与健康分会健康卫生科研项目(jkws201833)
关键词
溃疡性结肠炎
葡聚糖硫酸钠
普拉梭菌
TOLL样受体4
Ulcerative colitis
Dextran sulfate sodium salt
Faecalibacterium prausnitzii
Toll-like receptor 4
作者简介
赵翠娟(1981-),女,硕士研究生,副主任医师,主要研究方向:炎症性肠病及脂肪性肝病;通信作者:陈强,E⁃mail:chenq2006125@163.com
