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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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2010年5月11日, 赵玉沛院长、鲁重美书记为北京协和医院特需疑难病会诊中心揭牌。胰腺疾病专家组全体成员、部分职能处室负责人以及近20家媒体记者到场, 共同见证了这一时刻。挂牌仪式结束后, 全体专家前往“特需疑难病会诊中心”所在地, 为首例患者会诊, 媒体记者亦前往现场观摩了此次会诊。
一次挂号, 多个科室的顶级专家会诊, 这是北京协和医院新成立的特需疑难病会诊中心所提供的医疗服务。作为该中心首个挂牌并正式开诊的专病组, 胰腺疾病专家组汇聚了北京协和医院九大品牌科室、20余名顶级专家, 打造了一个国内最高水平的胰腺病诊治平台。这九大科室全部为国家重点学科和重点培育学科, 包括基本外科胰腺组、消化科、内分泌科、肿瘤内科、超声科、病理科、放射科、放疗科、核医学科, 而专家队伍也全部为国内本领域的著名专家。会诊专家团队采取A、B角的模式, 每次会诊各科至少保证1位专家参加。
北京协和医院特需疑难病会诊中心接收的患者主要包括三类:一是已就诊三个专科或在一个专科就诊多次尚未明确诊断者; 二是临床诊断较为明确, 但病情涉及多学科、多系统、多器官, 需要多个专科协同会诊者; 三是已在外院接受手术或其他治疗, 需要进一步确定治疗方案者。
北京协和医院作为卫生部指定的全国疑难重症诊治指导中心, 其优势在于构建了一个多学科、高水平、精尖技术的整体平台。仅以胰腺疾病为例, 基本外科赵玉沛教授牵头的“胰腺癌综合诊治方案的基础研究与临床应用”荣获2008年国家科技进步二等奖, 消化内科陆星华教授牵头的“胰腺癌流行病学、筛查方案及内镜治疗的基础和临床研究”荣获2008年中华医学科技奖二等奖, 在胰腺疾病方面代表了国内最高水平。
赵玉沛院长指出, 建立特需疑难病会诊中心, 是北京协和医院对有效开展跨学科协作诊疗活动所进行的, 可以使患者和医院双赢的组织运作模式的一种探索。对患者来说, 减少了等候时间、提高了诊治质量, 从根本上说是降低了医疗费用; 对医院来说, 可以大大促进各相关学科的发展、带动医生学术水平的整体提高, 促进医院培养全面思维的医学人才等。这样的调整, 也符合我国目前进行的新医改中有关大型公立医院的职责向集中解决疑难重症转化和调整的需要。
(北京协和医院宣传处 陈明雁)
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[1] Abraham C, Cho JH.Inflammatory bowel disease[J]. New Engl J Med, 2009, 361:2066-2078. DOI: 10.1056/NEJMra0804647
[2] Melgar S, Karlsson A, Michaelsson E.Acute colitis induced by dextran sulphate sodium progresses into chronicity in C57BL/6 but not in BALB/c mice-correlation between symptoms and inflammation[J]. Am J Physiol Gastrointest Liver Physiol, 2005, 288:G1328-G1338. DOI: 10.1152/ajpgi.00467.2004
[3] Heller F, Fuss IJ, Nieuwenhuis EE, et al.Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13 -producing NK-T cells[J]. Immunity, 2002, 17:629-638. DOI: 10.1016/S1074-7613(02)00453-3
[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. DOI: 10.1016/0016-5085(90)90290-H
[5] Luk HH, Ko JK, Fung HS, et al.Delineation of the protective action of zinc sulfate on ulcerative colitis in rats[J]. Eur J Pharmacol, 2002, 443:197-204. DOI: 10.1016/S0014-2999(02)01592-3
[6] Ekstrom GM.Oxazolone-induced colitis in rats:effects of budesonide, cyclosporin A, and 5-aminosalicylic acid[J]. Scand J Gastroenterol, 1998, 33:174-179. DOI: 10.1080/00365529850166914
[7] Fausto SM, Aaron DL, Jesus KY.Role of cytokines in inflammatory bowel disease[J]. World Gastroenterol, 2008, 14:4280-4288. DOI: 10.3748/wjg.14.4280
[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. DOI: 10.4049/jimmunol.172.9.5664
[9] Choi SY, Hur SJ, An CS, et al.Anti-inflammatory effects of Inonotus 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 efficacy of therapeutic agents for ulcerative Colitis[J]. Pharmacol Sci, 2004, 96:307-313. DOI: 10.1254/jphs.FP0040214
[11] Dharmani P, Chadee K.Biologic therapies against inflammatory bowel disease:a dysregulated immune system and the cross talk with gastrointestinal mucosa hold the key[J]. Curr Mol Pharmacol, 2008, 1:195-212. DOI: 10.2174/1874467210801030195
[12] David QS, Stephan RT.Immunopathogenesis of inflammatory bowel disease[J]. World J Gastroenterol, 2008, 14: 390-400. http://doi.med.wanfangdata.com.cn/qk/wjg200803007
[13] Neurath MF, Finotto S, Glimcher LH.The role of Th1/Th2 polarization in mucosal immunity[J]. Nat Med, 2002, 8: 567-573 DOI: 10.1038/nm0602-567
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