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两种溃疡性结肠炎小鼠模型的构建及其炎症反应机制比较
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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