不同浓度葡聚糖硫酸钠诱导小鼠急性溃疡性结肠炎模型的评价  

Evaluation of acute ulcerative colitis model induced by different concentrations of dextran sodium sulfate in mice

作　　者：许和鹏 董伟波 魏伟[1] 常艳[1] Xu Hepeng;Dong Weibo;Wei Wei;Chang Yan(Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine,Ministry of Education,Rheumatoid Arthritis Research Center,Anhui Medical University,Hefei 230032)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,安徽医科大学类风湿关节炎研究中心,抗炎免疫药物安徽省协同创新中心,合肥230032

出　　处：《安徽医科大学学报》2023年第10期1627-1633,共7页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:2108085MH320);安徽省高校协同创新项目(编号:GXXT-2020-065)。

摘　　要：目的对1.5%和3.0%两种浓度葡聚糖硫酸钠(DSS)诱导急性溃疡性结肠炎(UC)模型进行比较,得到病死率低且经济高效的造模方案。方法将C57BL/6J小鼠随机均分为对照组、1.5%DSS组、3.0%DSS组。对照组小鼠饮用灭菌水,DSS组小鼠饮用相应浓度的DSS溶液,连续7 d。第8~14天小鼠全部饮用灭菌水。观测小鼠便血情况,计算第1~14天疾病活动指数、体质量下降百分比和存活率。第8天处死小鼠,计算脾脏指数,测量结肠长度;HE染色观察结肠组织病理变化;免疫组化法检测结肠组织紧密连接蛋白Claudin-1和Occludin表达;免疫荧光检测结肠组织巨噬细胞比例;ELISA法测定血清和结肠组织匀浆肿瘤坏死因子-α(TNF-α)的水平。结果与对照组比较,1.5%和3.0%DSS两组小鼠均显示出与人类UC类似的临床表现和病理学特征,结肠长度均缩短(P<0.01),结肠组织Claudin-1和Occludin表达均降低(P<0.01),脾脏指数均升高(P<0.01),结肠组织巨噬细胞比例均升高(P<0.01),血清和结肠组织匀浆TNF-α水平均升高(P<0.01)。1.5%DSS组小鼠14 d内存活率高于3.0%DSS组小鼠。结论给予小鼠1.5%浓度的DSS溶液饮用7 d可高效经济地建立急性UC模型。Objective To compare acute ulcerative colitis(UC)model induced by dextran sulfate sodium(DSS)at 1.5%and 3.0%concentrations and obtain a cost-effective modeling scheme with low mortality.Methods C57BL/6J mice were randomly divided into control group,1.5%and 3.0%DSS group.The mice in control group drank sterilized water and the mice in each group of DSS drank the corresponding concentration of DSS solution,all mice were treated for 7 days.And all mice drank sterilized water on day 8 to 14.The blood stool of mice was observed and the disease activity index,the percentage of body weight loss and the percent of survival of mice were calculated on day 1 to 14.Mice were sacrificed on day 8.The spleen index was calculated and the length of colon was measured;HE staining was used to observe the histopathological changes of colon;The expressions of tight junction protein Claudin-1 and Occludin in colon tissue were detected by immunohistochemistry;Immunofluorescence detected the ratio of macrophage in colon tissue;Levels of tumor necrosis factor-α(TNF-α)in serum and colon tissue homogenates were detected by ELISA.Results Compared with the control group,both mice of 1.5%DSS group and mice of 3.0%DSS group showed similar clinical and pathological features to human UC;The colon lengths were both shortened(P<0.01);The expressions of Claudin-1 and Occludin in colon tissue both decreased(P<0.01);Spleen index increased(P<0.01);The proportion of macrophages in colon tissue increased(P<0.01);Levels of TNF-αin serum and colon tissue homogenates both increased(P<0.01).The percent of survival of 1.5%DSS mice within 14 days was higher than that of 3.0%DSS mice.Conclusion The acute UC model can be established efficiently and economically by giving 1.5%concentration of DSS solution in mice for 7 days.

关 键 词：葡聚糖硫酸钠 急性溃疡性结肠炎 模型 

分 类 号：R574.621[医药卫生—消化系统] R965.1[医药卫生—内科学]