葡聚糖硫酸钠诱导C57BL/6J小鼠急性结肠炎模型的建立与评价  

Establishment and evaluation of a model of acute colitis induced by dextran sodium sulfate in C57BL/6mice

作　　者：徐丽红[1,2] 肖芳[3] 兰小琴[3] 何嘉怡[3] 丁强[3] 田德安[3] 郑勇[1,2] 

机构地区：[1]石河子大学 [2]石河子医学院第一附属医院消化内科,新疆医学博士研究生832008 [3]华中科技大学同济医学院同济医院消化内科,武汉430030

出　　处：《医学研究生学报》2014年第9期918-922,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81100264)

摘　　要：目的离子通道的表达和功能受损可能是引起炎症性肠病相关性腹泻的病理生理机制之一,合适的动物模型是探讨其中详细病理生理过程的关键。本实验建立葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的C57BL/6J小鼠急性结肠炎模型,并对其腹泻相关的临床指标、组织学指标、病理学指标及离子通道蛋白的表达进行评价。方法选择C57BL/6J小鼠,随机数字列表法分为模型组,对照组,每组6只。模型组饮用4%DSS溶液7d诱发急性结肠炎。对照组小鼠正常饮水,记录小鼠的体重、粪便含水量、粪便性状及便血情况。取小鼠全结肠,肉眼及光镜下观察结肠组织学和病理学变化,蛋白免疫印迹法检测结肠组织中离子通道SLC26A3蛋白表达。结果所有实验小鼠均存活。模型组实验结束时粪便含水量[(73.30±8.31)%]较实验开始时[(44.32±6.42)%]显著升高(P=0.004),血便、炎症活动指数DAI值(3.50±0.87)较实验开始时(1.0±0.00)显著上升(P=0.000),第5天起体重较开始时明显下降(P=0.001)。实验结束时模型组的结肠组织学大体评分(4.50±0.84)较对照组(0.16±0.14)升高(P=0.00),模型组结肠组织病理学炎症评分(3.6±0.5)较对照组(0.33±0.5)升高(P=0.002),结肠明显缩短(P<0.05),SLC26A3的蛋白表达明显下降。结论 4%DSS诱导的C57BL/6J小鼠急性结肠炎的肠道黏膜损伤和腹泻的特征与人类溃疡性结肠炎相似,离子通道蛋白SLC26A3的表达受损与腹泻同时存在,该模型可为开展关于炎症性腹泻中离子通道功能改变的机制研究提供支持。Objective The expression and impaired function of ion channels might be one of the pathophysiological mecha -nisms responsible for diarrhea in inflammatory bowel disease （ IBD） .Proper animal model is the key to explore detailed pathophysiolog-ical process.The purpose of this study was to build a rat model of acute colitis induced by dextran sodium sulfate （DSS） in C57BL/6 mice and evaluate diarrhea-associated clinical , histological , pathological parameters and expressions of ion channel protein . Methods C57BL/6J mice of model group were treated with 4%DSS solution for 7 days to induce acute colitis.Mice body weight, stool moisture, stool consistency and the degree of hematochezia were recorded .The histopathological changes of mice colon specimens were observed visually and microcosmically, and the ion channel SLC26A3 protein was detected by Western Blot . Results All experimental mice survived.In the experiment, compared with control group , bloody diarrhea and weight lose occurred in model group , along with increased stool moisture （[73.30 ±8.31]% after experiment vs [44.32 ±6.42]% before experiment, P=0.004）, and rapidly in-creased disease activity index （DAI） of acute colitis （[3.50 ±0.87] after experiment vs [1.0 ±0.00] before experiment, P=0.000）.At the end of this experiment , compared with control group , the model group resulted in higher colonic damage score and pathological inflammation score （P=0.00, P=0.002）, significantly shortened co-lon （P=0.00） and decreased expression of SLC26A3. Conclusion The intestinal mucosal injury and phenotypic features of 4%DSS-induced acute colitis are very similar to those of human ulcerative colitis .Impaired expression of intestinal ion transporter SLC26 A3 coexists with diarrhea in model group mice , and this model can support the research on mechanism of functional changes of ion channels in inflammatory diarrhea .

关 键 词：葡聚糖硫酸钠 炎症性肠病 动物模型 SLC26A3 

分 类 号：R574.62[医药卫生—消化系统]