两种UC小鼠模型的病理损伤和肠道菌群对比研究  

Comparative study of intestinal flora and histopathological damage in mice with ulcerative colitis induced by DSS and TNBS

作　　者：谌雪梅 彭西 叶俏波[3] 叶臻 邓庆 王娟[1] 温昌琳 袁施彬[1] SHEN Xuemei;PENG Xi;YE Qiaobo;YE Zhen;DENG Qin;WANG Juan;WEN Changlin;YUAN Shibin(College of Life Science,China West Normal University,Nanchong 637002,China;College of Pharmacy,Chengdu University,Chengdu 610106;School of Basic Medicine,Chengdu University of TCM,Chengdu 611137;Si Chuan Youngster Technology Co.,Ltd,Chengdu 611135)

机构地区：[1]西华师范大学生命科学学院,四川南充637002 [2]成都大学药学院,成都610106 [3]成都中医药大学基础医学院,成都611137 [4]四川扬克斯特科技有限公司,成都611135

出　　处：《中国实验动物学报》2021年第6期758-767,共10页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金(81973742);四川省教育厅科研创新团队(自然科学)项目(17TD0037);西华师范大学英才基金项目(17YC357)。

摘　　要：目的用葡聚糖硫酸钠(DSS)和2,4,6-三硝基苯磺酸(TNBS)构建小鼠溃疡性结肠炎模型,对比研究临床症状、结肠组织病理损伤和结肠菌群构成。方法C57BL/6雄性小鼠30只,随机分为对照组、DSS组和TNBS组。造模期7 d。每日监测临床症状,包括体重和粪便隐血,造模结束时取结肠做组织病理诊断,使用16S rDNA测序技术检测结肠内容物的菌群组成。结果临床显示,DSS组从第3天开始排软便,第5天粪便隐血阳性,体重下降;TNBS组第2天体重下降,造模前4 d排软便和稀便,且粪便隐血阳性。剖检显示,两个模型组的结肠重量均增加,仅DSS组结肠显著变短。组织病理学上,DSS组结肠溃疡灶部位固有结构破坏及临近隐窝扩张,TNBS组溃疡灶中见隐窝结构存留及隐窝细胞增生。两个模型组结肠菌群紊乱的特征存在差异。与对照组比较,软壁菌门和蓝藻菌门的丰度在DSS组无显著性变化而在TNBS组增加(P<0.05);酸杆菌门丰度在DSS组无显著性变化而在TNBS组显著降低(P<0.05);放线菌门和乳杆菌属的丰度在DSS组降低(P<0.05)在TNBS组无显著性变化;拟杆菌属在DSS组丰度上升而在TNBS组显著下降(P<0.05)。结论DSS和TNBS乙醇诱导的UC模型在临床症状、结肠组织病理损伤特征和肠道菌群结构既有共性,也有其自身特点。研究结果可为动物模型选择提供一定的理论参考。Objective Mouse models of ulcerative colitis(UC)were established with sodium dextran sulfate(DSS)and 2,4,6-trinitrobenzene sulfonic acid(TNBS)to compare the differences in clinical symptoms,pathological lesions and colonic flora.Methods Thirty male C57 BL/6 mice were randomly divided into a control group,DSS group and TNBS group.The modeling period was 7 days.Clinical symptoms,including body weight and fecal occult blood,were monitored daily.The colon was harvested at the end of modeling for histopathological diagnosis,and 16 S rDNA sequencing technology was used to detect the bacterial composition of the colon contents.Results The clinical result showed that DSS induced diarrhea three days after treatment,fecal occult blood was positive,and body weight was decreased on the fifth day.TNBS treatment decreased body weight on the second day,soft and loose stools were observed from the first to the fourth day,and fecal occult blood was positive.At necropsy,the colon weight in both model groups was increased,whereas the colon in the DSS group was significantly shorter.Histopathologically,the ulcer foci in the colon exhibited a damaged histological structure,and the nearby crypts were dilated in the DSS group,whereas residual crypts accompanied by obvious cell proliferation were observed in the ulcer foci of the TNBS group.The characteristics of colon flora disturbances in the two model groups were different.Compared with the control group,the abundances of Tenericutes and Cyanobacteria were not significantly altered in the DSS group but were increased in the TNBS group(P<0.05).The abundance of Acidobacteria was unchanged in the DSS group but significantly decreased in the TNBS group(P<0.05).The abundance of Actinobacteria and Lactobacillus was significantly decreased in the DSS group but unchanged in the TNBS group(P<0.05).The abundance of Bacteroidetes was significantly increased in the DSS group but decreased in the TNBS group(P<0.05).Conclusions The UC models induced by DSS and TNBS/ethanol showed similar character

关 键 词：溃疡性结肠炎 肠道菌群 病理组织损伤 16S rDNA DSS TNBS 

分 类 号：Q95-33[生物学—动物学]