苗政;钱家鸣;李景南;唐晓艳;杨晓鸥;
MIAO Zheng,QIAN Jia-ming,LI Jing-nan,TANG Xiao-yan,YANG Xiao-ou Department of Gastroenterology,Peking Union Medical College Hospital,Chinese Academyof Medical Science & Peking Union Medical College,Beijing 100730,China

• 1:中国医学科学院北京协和医学院北京协和医院消化内科

摘要(Abstract)：

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)0.2ml2d,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0.2ml2d,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。
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.

关键词(KeyWords)： 溃疡性结肠炎;葡聚糖硫酸钠;恶唑酮;白细胞介素-4;干扰素-γ;肿瘤坏死因子-α;核因子κB
ulcerative colitis; dextransulfatesodium; oxazolone; interleukin 4; interferon-γ; tumor necrosis factor-α; nuclear factor-Kappa B

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 苗政;钱家鸣;李景南;唐晓艳;杨晓鸥;
MIAO Zheng,QIAN Jia-ming,LI Jing-nan,TANG Xiao-yan,YANG Xiao-ou Department of Gastroenterology,Peking Union Medical College Hospital,Chinese Academyof Medical Science & Peking Union Medical College,Beijing 100730,China

参考文献(References)：

• [1]Abraham C,Cho JH.Inflammatory bowel disease[J].New Engl J Med,2009,361:2066-2078.
• [2]MelgarS,Karlsson A,Michaelsson E.Acute colitis induced by dextran sulphate sodium progresses into chronicity in C57BL/6but not in BALB/c mice-correlation between symptoms and inflammation[J].Am J Physiol Gastrointest Liver Physiol,2005,288:G1328-G1338.
• [3]Heller F,Fuss IJ,Nieuwenhuis EE,et al.Oxazolone coli-tis,a Th2colitis model resembling ulcerative colitis,is me-diated by IL-13-producing NK-T cells[J].Immunity,2002,17:629-638.
• [4]Okayasu I,Hatakeyama S,Yamada M,et al.A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice[J].Gastroenterology,1990,98:694-702.
• [5]Luk HH,Ko JK,Fung HS,etal.Delineation of the protec-tive action of zinc sulfate on ulcerative colitis in rats[J].Eur J Pharmacol,2002,443:197-204.
• [6]Ekstrom GM.Oxazolone-induced colitis in rats:effects of budesonide,cyclosporin A,and5-aminosalicylic acid[J].Scand J Gastroenterol,1998,33:174-179.
• [7]Fausto SM,Aaron DL,Jesus KY.Role of cytokines in in-flammatory bowel disease[J].World Gastroenterol,2008,14:4280-4288.
• [8]Forbes E,Murase T,Yang M,et al.Immunopathogenesis of experimental ulcerative colitis is mediated by eosinophil peroxidase[J].J Immunol,2004,172:5664-5675.
• [9]Choi SY,Hur SJ,An CS,et al.Anti-inflammatory effects ofInonotus obliquus in colitis induced by dextran sodium sulfate[J].Biomed Biotechnol,2010-03-10[Epub ahead of print].http://www.hindawi.com/journals/jbb/.
• [10]Ryotaro K,Satoko K,Tomiko O,et al.Oxazolone-induced Colitis in BALB/C mice:a new method to evaluate the effi-cacy of therapeutic agents for ulcerative Colitis[J].Phar-macol Sci,2004,96:307-313.
• [11]Dharmani P,Chadee K.Biologic therapies against inflamma-tory bowel disease:a dysregulated immune system and the cross talk with gastrointestinal mucosa hold the key[J].Curr Mol Pharmacol,2008,1:195-212.
• [12]David QS,Stephan RT.Immunopathogenesis of inflammato-ry bowel disease[J].World J Gastroenterol,2008,14:390-400.
• [13]Neurath MF,Finotto S,Glimcher LH.The role of Th1/Th2polarization in mucosal immunity[J].Nat Med,2002,8:567-573.