DSS诱导小鼠溃疡性结肠炎模型的动态评估  

Dynamic evaluation of a mouse model of DSS induced ulcerative colitis

作　　者：李富凤[1] 王汝俊[1] 潘华新[1] 巫燕莉[1] 李燕舞[1] 

机构地区：[1]广州中医药大学脾胃研究所,广东省广州市510405

出　　处：《世界华人消化杂志》2015年第11期1721-1727,共7页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81202627~~

摘　　要：目的:通过葡聚糖硫酸钠(dextran sulfate sodium,D S S)诱导建立小鼠溃疡性结肠炎(ulcerative colitis,UC)急、慢性模型,并动态监测小鼠结肠损伤、病理变化及血浆、结肠黏膜中白介素(interleukin,IL)-1β、I L-18、I L-33等细胞因子的变化,以评估该模型.方法:64只C57BL/6小鼠随机分为正常组和模型组.模型组采用3%DSS(分子量36000-50000)饮水1 wk造成结肠损伤,再恢复正常饮水3 wk,分别于第1、2、3、4周4个时间点对小鼠进行动态观察:小鼠粪便性状改变;结肠长度及结肠质量变化;结肠病理变化;结肠黏膜炎症评分;血浆与结肠黏膜中IL-1β、IL-18、IL-33变化.结果:造模1 wk后,小鼠出现腹泻、血便、懒动、蜷缩成堆,病理观察见结肠上皮糜烂、出血、多病灶浅溃疡,大量炎性细胞浸润黏膜及黏膜下层;与正常组相比,模型组结肠质量增加(P<0.05),结肠长度缩短(P<0.01),结肠黏膜炎症评分明显增高(P<0.01);血浆和结肠黏膜中炎症因子I L-1β、IL-18、IL-33的含量显著升高(P<0.05、P<0.01);造模2 wk后,模型小鼠血便逐渐减少,结肠黏膜下可见大量炎细胞浸润,结肠质量增高(P<0.01),结肠长度减少(P<0.01),结肠黏膜炎症评分增高(P<0.01),血浆中IL-1β、I L-18的浓度与结肠黏膜中I L-18的浓度仍明显高于正常组(P<0.05);造模后3、4wk,小鼠活动及粪便性状恢复正常,结肠黏膜仍可见炎细胞浸润,肌纤维排列紊乱,结肠质量增加(P<0.01),结肠长度缩短(P<0.01),黏膜炎症评分、血浆与结肠黏膜中IL-1β、IL-18、IL-33含量与正常组比较差异无统计学意义(P>0.05).结论:上述指标的动态监测结果在一定程度上体现了DSS诱导的小鼠UC模型从急性到慢性的病理变化过程,可以为临床及相关药物作用研究提供病理模型.AIM： To develop an experimental mouse model of ulcerative colitis（UC） and to dynamically monitor the colonic injures, pathological changes, and contents of interleukin（IL）-1β, IL-18, and IL-33 in plasma and colonic mucosa to evaluate the model.METHODS： Sixty-four C57BL/6 mice wererandomly divided into either a normal group or a model group. The model group was fed 3% dextran sulfate sodium（DSS） solution for a week, followed by normal drinking water for another 3 wk. We then dynamically observed fecal condition, alterations of colon length and weight, pathological changes, colonic mucosa inflammation score and contents of IL-1β, IL-18, and IL-33 in plasma and colonic mucosa every week.RESULTS： One week after modeling, the mice developed diarrhea, bloody stools, crouching, and huddled together. Pathological examination showed colon epithelial erosion, bleeding, multifocal ulcers and numerous inflammation cells infiltrating the mucosa and submucosa. Compared to the normal group,the colon weight was markedly increased（P 〈 0.05）, the colon length was significantly shortened（P 〈 0.01）, the colonic mucosa inflammation score was significantly increased（P 〈 0.01）, and the contents of IL-1β, IL-18, and IL-33 in both plasma and mucosa were significantly elevated（P 〈 0.05, P 〈 0.01） in the model group. At the end of the second week, compared to the normal group, the model group had gradually decreased bleeding, a large number of inflammatory cells in the submucosa, increased colon weight（P 〈 0.01）, shortened colon length（P 〈 0.01）, increased colonic mucosa inflammation score（P 〈 0.01）, and dramatically elevated contents of IL-1β and IL-18 in plasma and IL-18 in colonic mucosa（P 〈 0.05）. At the third and fourth weeks, the mouse activity and fecal condition returned to normal, inflammation cells could be seen in colonic mucosa, muscle fiber wasarranged disorderly; compared to normal group, colon weight was increased（P 〈 0.01）, colon length was shorte

关 键 词：右旋葡聚糖硫酸钠 C57BL/6 溃疡性结肠炎 白介素-1β 白介素-18 白介素-33 

分 类 号：R574.62[医药卫生—消化系统] R-332[医药卫生—内科学]