结肠灵通过调节NLRP3炎性小体活化对感染后肠易激综合征大鼠内脏敏感性的机制研究  

Study on the mechanism of Jiechangling on the visceral sensitivity of post-infection irritable bowel syndrome rats by regulating NLRP3 inflammatory body activation

作　　者：韩棉梅[1] 马军[1] 宋雨鸿[1] 梁嘉恺[2] HAN Mianmei;MA Jun;SONG Yuhong;LIANG Jiakai(Department of TCM,Guangzhou First People’s Hospital,Guangzhou 510180;Department of Quality Control,the Second Affiliated Hospital of Guangzhou Medical University,China)

机构地区：[1]广州市第一人民医院中医科,广东广州510180 [2]广州医科大学附属第二医院质控科

出　　处：《胃肠病学和肝病学杂志》2020年第10期1145-1150,共6页Chinese Journal of Gastroenterology and Hepatology

基　　金：广东省中医药局科研课题(20171193)。

摘　　要：目的探讨核苷酸结合寡聚化结构域样受体3(NLRP3)炎症小体在结肠灵调节感染后肠易激综合征(PI-IBS)内脏高敏感性中的作用及分子机制。方法选取SPF级雄性SD大鼠40只随机分配到4组:正常对照组、模型组、结肠灵组和阳性对照组。HE染色检测大鼠结肠组织中性粒细胞等炎症细胞浸润情况及黏膜损伤状况;利用腹壁回缩反射(AWR)评分和粪便含水量评估大鼠的内脏敏感性。ELISA检测大鼠血清中IL-18和IL-1β表达;Western blotting检测NLRP3、ASC、Caspase-1、IL-18、IL-1β及NF-κB表达。结果正常对照组大鼠结肠黏膜完整,无炎症细胞浸润;模型组大鼠结肠黏膜受损,有大量炎症细胞(中性粒细胞等)浸润,AWR评分值显著升高(P<0.01),粪便含水量也显著增加(P<0.01);给予药物干预后黏膜组织完整性恢复,降低了炎症细胞浸润,AWR评分值和大鼠粪便含水量显著降低(P<0.05)。结肠灵干预降低了大鼠血清中IL-18和IL-1β含量(P<0.05),显著抑制NLRP3、ASC、Caspase-1、IL-18、IL-1β及NF-κB蛋白表达(P<0.05)。结论结肠灵可能通过NF-κB通路抑制NLRP3炎症小体活化,降低大鼠结肠黏膜炎症,改善PI-IBS大鼠内脏敏感性。Objective To investigate the role and molecular mechanism of NLRP3 inflammatory body in Jiechangling to regulate visceral hypersensitivity of post-infection irritable bowel syndrome(PI-IBS).Methods Forty SPF male SD rats were randomly assigned to 4 groups:normal control group,model group,Jiechangling group and positive control group.HE staining was used to detect the infiltration of inflammatory cells,such as neutrophils and mucosal damage in rat colonic tissues.The abdominal withdrawal reflex(AWR)score and fecal water content were used to evaluate the intestinal sensitivity of rats.ELISA was used to detect the expression of IL-18 and IL-1βin rat serum;Western blotting was used to detect the expression of NLRP3,ASC,Caspase-1,IL-18,IL-1βand NF-κB.Results The colon mucosa of the control group was intact and there was no inflammatory infiltration.The colon mucosa of the model group was damaged with a large number of inflammatory cells(neutrophils,etc.)infiltration,and the AWR score was significantly increased(P<0.01),fecal water content was also increased significantly(P<0.01);mucosal tissue integrity was restored after drug intervention,reducing inflammation and infiltration,AWR scores,and fecal water content in rats were significantly reduced in rats(P<0.05).Jiechangling intervention reduced the levels of IL-18 and IL-1βin rat serum(P<0.05),and significantly inhibited the expression of NLRP3,ASC,caspase-1,IL-18,IL-1βand NF-κB protein(P<0.05).Conclusion Jiechangling may inhibit the activation of NLRP3 inflammatory body through the NF-κB pathway,reduce inflammation of colonic mucosa in rats,and improve visceral sensitivity in PI-IBS rats.

关 键 词：肠易综合征 结肠灵 NLRP3炎性小体 IL-18 IL-1Β 

分 类 号：R574[医药卫生—消化系统]