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慢性溃疡性结肠炎小鼠疾病活动度、组织病理及细胞因子动态变化分析OA北大核心CSTPCD

Dynamic changes to disease activity,histopathology,and cytokines in mice with chronic ulcerative colitis

中文摘要英文摘要

目的 分析慢性溃疡性结肠炎(ulcerative colitis,UC)小鼠疾病活动度、结肠炎症和组织病理及血清细胞因子水平的动态变化.方法 2.5%葡聚糖硫酸钠(诱导)+饮用水(缓解)各5 d自由饮用为1个周期,重复3个周期.记录疾病活动指数、结肠长度及组织病理损伤等,检测结肠髓过氧化物酶(myeloperoxidase,MPO)、血清和结肠IL-1β等细胞因子含量.结果 在3个周期中,小鼠疾病活动度和结肠长度缩短现象在诱导期加重、缓解期减轻.第2和3周期便血时间提前,便血小鼠数量增多,体重短暂低幅度降低后迅速回升.第1和3周期结肠组织病理损伤程度和MPO含量在诱导期升高、缓解期降低,升降幅度低于DAI值变化幅度;在第2周期缓解期升高.在诱导中,脾指数、血清IL-1β、IL-6和IL-17A含量持续升高,实验结束时均高于正常组;TNF-α水平在诱导期升高、缓解期降低,IL-10变化趋势与TNF-α相似;TGF-β含量先升高后降低,第3周期结束后高于正常组.结肠IL-6、IL-1β和IL-17A的含量呈现相似的先升高后降低趋势;TNF-α含量无明显变化;IL-10含量在诱导期降低、缓解期升高.结论 在慢性UC诱导过程中,小鼠便血症状和全身性炎症反应逐渐加重,在死亡率、体重和结肠组织病理学损伤表现出逐渐增强的耐受力和恢复能力,结肠组织病理学损伤的发生和缓解滞后于症状变化,结肠炎症逐渐转变为以PMN活化为主的模式.

Objective To analyze the dynamic changes to disease activity,colonic inflammation,histopathology,and serum cytokine levels in mice with chronic ulcerative colitis(UC).Methods For UC induction,2.5%dextran sodium sulfate solution was provided ad libitum for 5 days,and to model remission,tap water was supplied for another 5 days in one induction cycle.Disease activity index(DAI),colon length,and pathological changes to colon tissue were determined.The levels of myeloperoxidase(MPO)in colon tissue and of cytokines such as IL-1 β in serum and colon were detected.Results During the three cycles,disease activity was aggravated and colon length shortened in mice during the induction periods,both of which were relieved during the remission periods.The blood appeared was observed in the stool was earlier in cycles 2 and 3.The number of mice with stool blood increased,and their body weight decreased by a small amount briefly,then recovered rapidly.The degree of histopathological damage to the colon and MPO content in cycles 1 and 3 increased in the induction periods and decreased in the remission periods,with the magnitude of change smaller than that of the change in DAI values;and they increased in the remission period of cycle 2.During induction,the spleen index and serum levels of IL-1β,IL-6,and IL-17A increased continuously and were higher than those in the control group at the end of the experiment.Levels of TNF-α were increased in the induction periods and decreased in the remission periods,and the trend in IL-10 change was similar to that of TNF-α.TGF-β content increased and then decreased and was higher than that in the control group at the end of cycle 3.The colon contents of IL-1β,IL-6,and IL-17A showed similar trends of increasing and then decreasing,but there was no significant change in colon TNF-α.The concentration of IL-10 decreased during the induction periods and increased during the remission periods.Conclusions During the induction of chronic UC in mice,the symptoms of hematochezia and systemic inflammatory reactions gradually increased,and the mice showed an increase in tolerance and ability to resist mortality,weight loss,and histopathological injury to the colon.The onset and remission of colonic histopathological damage lags behind symptomatic changes,and there is a gradual shift in colonic inflammation to a pattern dominated by polymorphonuclear neutrophils(PMN)activation.

孔维姣;晏乙月;赵佩凯;毛晓健;王亭

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,昆明 650500

溃疡性结肠炎慢性模型葡聚糖硫酸钠细胞因子中性粒细胞

ulcerative colitischronic modeldextran sulfate sodiumcytokinesneutrophil

《中国比较医学杂志》 2024 (006)

18-27 / 10

国家自然科学基金项目(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(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).

10.3969/j.issn.1671-7856.2024.06.003

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