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Establishment of Two Murine Models of Ulcerative Colitis and Comparison of the Mechanism of Colitis-related Inflammatory Reactions
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摘要:目的 构建葡聚糖硫酸钠(dextransulfatesodium, DSS)以及恶唑酮(oxazolone, OXZ)诱导的小鼠溃疡性结肠炎模型, 比较两种模型中炎症因子水平的变化, 评价两种模型。方法 12只C57BL小鼠, 随机分为两组, DSS模型组(n=8)予3%DSS自由饮用5d, DSS对照组(n=4)饮用蒸馏水5d, 第6天处死两组小鼠。8只BALB/C小鼠, 随机分为两组, OXZ模型组(n=4)予皮肤涂抹3%OXZ(100%乙醇溶剂)0.2ml 2d, 5d后以0.8%OXZ(50%乙醇溶剂)0.15ml灌肠; OXZ对照组予皮肤涂抹100%乙醇0.2ml 2d, 5d后以50%乙醇0.15ml灌肠, 灌肠后第3天处死两组小鼠。观察各组小鼠疾病活动指数(disease activity index, DAI)、结肠组织大体评分和病理评分, 并检测小鼠结肠组织中髓过氧化物酶(myeloperoxidase, MPO)、白细胞介素-4(interleukin4, IL-4)、干扰素-γ(interferon-γ, IFN-γ)、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、核因子κB(nuclear factor-Kappa B, NF-κB)的水平。结果 两种模型组小鼠DAI、组织大体评分和病理评分均较对照组有明显改变; DSS结肠炎、OXZ结肠炎均可导致MPO、TNF-α、NF-κB明显上升, DSS结肠炎IFN-γ明显上升, OXZ结肠炎IL-4明显上升。结论 DSS及OXZ均能诱导出小鼠溃疡性结肠炎模型, 其中OXZ诱导的小鼠溃疡性结肠炎是Th2型炎症反应, 更接近人类溃疡性结肠炎。Abstract:Objective To establish two murine models of ulcerative colitis (UC) and explore the mechanism of colitits-related inflammatory reactions.Methods Totally 12 C57BL mice were randomly divided into two groups:dextransulfatesodium (DSS) model group (n=8, allowed to drink 3% DSS for 5 days) and DSS control group (n=4, allowed to drink water for 5 days). In addition, 8 BALB/C mice were randomly divided into oxazolone (OXZ) model group(n=4, mice were skin-sensitized with 3% OXZ 0.2 ml in 100% ethanol for 2 days followed by intrarectal administration of 0.8% OXZ 0.15 ml in 50% ethanol 5 days later) and OXZ control group(n=4, mice were skin-sensitized with 100% ethanol for 2 days followed by intrarectal administration of 50% ethanol 0.15 ml 5 days later). The disease activity index (DAI), tissular general score, and histological score were calculated. The levels of myeloperoxidase (MPO), interleukin 4 (IL-4), interferon-γ (INF-γ), tumor necrosis factor-α(TNF-α), and nuclear factor-Kappa B (NF-κB) in the colon tissue were determined.Results DAI, tissular general score, and histological score were significantly different in either DSS or OXZ model group when compared with their control groups. MPO, TNF-α, and NF-κB significantly increased in DSS and OXZ model groups. In addition, INF-γ significantly increased in DSS model group and IL-4 significantly increased in OXZ model group.Conclusions Both DSS and OXZ can induce ulcerative colitis in mice. OXZ-induced murine colitis is highly associated with T helper cell type 2 (Th2), which is more similar to human UC.
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世界初级创伤救治(Primary Trauma Care，PTC)理事会于2012年3月28日在阿根廷首都布宜诺斯艾利斯市召开了理事会议，来自卫生部医院管理研究所的阎赢主任和霍添琪，北京协和医院急诊科于学忠教授、王仲教授和麻醉科黄宇光教授出席了此次会议。会议回顾了PTC在全球近50个国家开展工作的情况，包括PTC在中国实施的成功经验。在卫生部医政司和医院管理研究所的领导下，PTC理事会与中国医师协会急诊医师分会、麻醉学医师分会联手合作，自2010年9月5日在中国成功启动PTC，至今已经在全国15个省份为2000多家医院培训了6000多名医学专业人员，取得了良好的培训效果。北京协和医院作为中国医师协会急诊医师分会和麻醉学医师分会的会长单位，为该项目做出了积极贡献。作为PTC理事，黄宇光教授代表中方团队介绍了PTC多学科全方位合作的中国模式。目前中国已经成为PTC项目培训在全球规模最大的国家，受到各位PTC理事和与会代表的好评。会议对如何促进PTC项目持续发展和相关教材的修订进行了讨论，并且决定PTC世界大会将于2013年在中国召开。
(卫生部医院管理研究所 霍添琪)
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