葡聚糖硫酸钠诱导小鼠慢性溃疡性结肠炎模型进展观察
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云南中医药大学中药学院暨云南省南药可持续利用研究重点实验室

基金项目:

国家自然科学(编号:82360810, 81960750, 81760745);云南省科技厅-云南中医药大学应用基础研究联合专项重点项目(编号:202001AZ070001-004);云南省科技人才和平台计划(202305AC160039, 202105AG070012);云南(昆明)杨国源专家工作站(YSZJGZZ-2020037);云南省王源超专家工作站(202305AF150018)


Observation on the progress of the murine models of chronic ulcerative colitis induced by dextran sodium sulfate
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College of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization,Yunnan University of Chinese Medicine

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    摘要:

    目的 以葡聚糖硫酸钠(DSS)诱导小鼠慢性溃疡性结肠炎(UC),观察模型进展情况。方法 2.5%DSS+饮用水各5天自由饮用为1个周期,重复3个周期。记录疾病活动指数(DAI)、结肠长度及组织病理损伤、脏器指数等,检测结肠髓过氧化物酶(MPO)、血清和结肠IL-1β等细胞因子含量。结果 在3个周期中,小鼠均出现腹泻、便血和体重减轻,结肠长度缩短和病理损伤,给予DSS后加重,给予饮用水后缓解;结肠MPO含量逐渐升高;脾指数和血清IL-1β、IL-6、IL-17A、TGF-β和TNF-α水平持续或波动升高;结肠IL-1β、IL-6、IL-17A含量第1或2周期显著升高,后缓慢降低;结肠TNF-α无明显变化;血清和结肠IL-10含量呈上下波动,实验结束时较正常组降低或持平。结论 本方法可诱导慢性UC,表现为症状“发作-缓解”交替,以及持续的全身性炎症反应和结肠中性粒细胞过度激活,一定程度反映了UC反复发作的特点,可作为UC病理变化特征和干预时机分析,以及UC治疗药物发现和评价的工具。

    Abstract:

    Objective To investigate the progress of chronic Ulcerative Colitis (UC) model induced by dextran sulfate (DSS) in mice. Methods 2.5% DSS solution were provided ad libitum for 5 days, and tap water for were supplied for another 5 days in one induction cycle. Male C57BL/6 mice were undergone continuous three cycles of induction to establish the chronic UC model. The weight, disease activity index (DAI), organ index, colon length of mice and pathological changes of colon tissue were determined. The level of myeloperoxidase (MPO) in colon tissue, cytokines such as IL-1β in serum and colon were detected. Results During the three cycles, all mice had diarrhea, bloody stool, weight loss, colon length shortening and pathological injury, which were aggravated after DSS administration and relieved after drinking water administration. The content of MPO in colon gradually increased. The spleen index and the levels of IL-1β, IL-6, IL-17A, TGF-β and TNF-α in serum increased continuously or fluctuating. The contents of IL-1β, IL-6 and IL-17A in colon increased significantly in the first or second cycle, and then decreased slowly. There was no significant change in TNF-α in colon. The concentrations of IL-10 in serum and colon fluctuated up and down, and decreased to a level lower than or remained the same as that in normal group at the end of the experiment. Conclusion Chronic UC model can be successfully induced by 2.5%DSS solution, which is characterized by alternating symptoms of "attack-remission". The persistent systemic inflammatory reaction and overactivation of colonic neutrophils reflect the characteristics of recurrent UC to some extent. It can be used as a tool for analying the pathological changes and interrention opportunities of UC, as well as for discovering and evaluating UC therapeutic drugs.

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  • 收稿日期:2023-09-26
  • 最后修改日期:2024-04-16
  • 录用日期:2024-05-30
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