CAJ | 학술논문

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C57 BL/6 J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7 d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 SLC26 A3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。
목적：리자통도적표체화공능수손가능시인기염증성장병상관성복사적병리생리궤제지일，합괄적동물모형시탐토기중상세병리생리과정적관건。본실험건립포취당류산납（ dextran sodium sulfate ， DSS）유도적C57BL/6J소서급성결장염모형，병대기복사상관적림상지표、조직학지표、병이학지표급리자통도단백적표체진행평개。방법선택C57 BL/6 J소서，수궤수자렬표법분위모형조，대조조，매조6지。모형조음용4％DSS용액7 d유발급성결장염。대조조소서정상음수，기록소서적체중、분편함수량、분편성상급편혈정황。취소서전결장，육안급광경하관찰결장조직학화병이학변화，단백면역인적법검측결장조직중리자통도 SLC26 A3단백표체。결과소유실험소서균존활。모형조실험결속시분편함수량[（73．30±8．31）％]교실험개시시[（44．32±6．42）％]현저승고（P＝0．004），혈편、염증활동지수DAI치（3．50±0．87）교실험개시시（1．0±0．00）현저상승（P＝0．000），제5천기체중교개시시명현하강（P＝0．001）。실험결속시모형조적결장조직학대체평분（4．50±0．84）교대조조（0．16±0．14）승고（P＝0．00），모형조결장조직병이학염증평분（3．6±0．5）교대조조（0．33±0．5）승고（P＝0．002），결장명현축단（P＜0．05），SLC26A3적단백표체명현하강。결론4％ DSS유도적C57BL/6J소서급성결장염적장도점막손상화복사적특정여인류궤양성결장염상사，리자통도단백SLC26A3적표체수손여복사동시존재，해모형가위개전관우염증성복사중리자통도공능개변적궤제연구제공지지。
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 .