葡聚糖硫酸钠诱导的小鼠肠炎模型中炎性因子的变化

Regularity of Inflammatory Cytokines Change in DSS-Induced Colitis Mouse Model

目的 通过建立葡聚糖硫酸钠（DSS）诱导的小鼠肠炎模型,观察其炎性因子变化规律.方法 选用C57BL/6雄性小鼠,随机分为DSS组与对照组,DSS组给予3%的DSS溶液自由饮用7d,对照组自由饮水.每天观察小鼠体重、便血、腹泻情况并进行DAI评分;于7d时处死小鼠,观察小鼠肠道形态学的变化;通过组织病理学技术分析肠绒毛长度、肠隐窝数量的变化;通过流式细胞微球芯片捕获技术检测小鼠血清中炎性细胞因子水平的变化.结果 与对照组比较,DSS组小鼠出现明显的体重下降、便血、腹泻等症状,活动度及精神状态变差,DAI评分升高;小鼠肠道充血严重、大肠明显缩短;组织病理切片显示小鼠结肠隐窝结构破坏、减少、绒毛断裂、可见大量的炎性细胞浸润;小鼠血清中促炎性细胞因子IL-6、TNF-α上升,抗炎性细胞因子IL-10明显下降.结论 抗炎性因子与促炎性因子失衡可能是炎性肠病的重要机制.

Objective To observe the changes of the pathological damage and inflammatory cytokine production in the DSS-induced colitismouse model. Methods The male C57BL/6 mice were fed 3% （wt/vol） DSS dissolved in distilled water from day 0 to 7 to induce colitis. Animal body weight change, occult or gross rectal bleeding, and stool consistency were monitored for each mouse. The resultant inflammatory bowl disease （IBD） DAI represents the average of the scores of the colitis symptoms. Mice were sacrificed at day 7 after administration of DSS and the changes of intestinal morphology were observed. The pathological changes such as length of villi, number of crypt were analyzed by histopathological technique. The changes of inflammatory cytokines in the serum of mice were analyzed by Cytometric Bead Array. Results DSS-treated mice had obvious weight loss, diarrhea, and blood in the stool. The DAI scorewas also significantly increased. The colon length were shorter. Distortion of crypt architecture, inflammatory cell infiltration ofinflammatory cell, the number of LGR5＋ intestinal stem cells decreased. Levels of pro-inflammatory cytokines in serum such as IL-6, TNF-αwere increased. Levels of anti- inflammatory cytokine IL-10 was declined obviously. Conclusion DSS-induced colitis mouse model was successfully established, confirming the imbalances between anti-inflammatory cytokines and pro-inflammatory cytokines and the absence of LGR5＋ stem cells in the crypt are important mechanisms of IBD.