结肠炎小鼠模型的病理机制研究

doi:10.3969/j.issn.1006-7795.2018.05.015

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (5): 704-709.doi: 10.3969/j.issn.1006-7795.2018.05.015

结肠炎小鼠模型的病理机制研究

杨敏¹, 安国^2,5, 赵威^3,5, 马媛媛^4,5

1. 首都医科大学附属北京世纪坛医院干部综合科, 北京 100038;
2. 北京大学肿瘤医院暨北京市肿瘤防治研究所实验动物室, 北京 100142;
3. 北京大学肿瘤医院暨北京市肿瘤防治研究所细胞生物室, 北京 100142;
4. 北京大学肿瘤医院暨北京市肿瘤防治研究所胸外二科, 北京 100142;
5. 恶性肿瘤发病机制及转化研究教育部重点实验室, 北京 100142

收稿日期:2018-01-04 出版日期:2018-09-21 发布日期:2018-10-20
通讯作者: 马媛媛 E-mail:mayynmg@aliyun.com
基金资助:
国家自然科学基金（81502578，81872025），首都医科大学附属北京世纪坛医院中青年学科骨干培养专项科学研究基金资助（2016-QB11）。

Pathological mechanism study on the colitis mice model

Yang Min¹, An Guo^2,5, Zhao Wei^3,5, Ma Yuanyuan^4,5

1. Department of Gerontology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China;
2. Department of Laboratory Animal, Peking University Cancer Hospital & Institute, Beijing 100142, China;
3. Department of Cell Biology, Peking University Cancer Hospital & Institute, Beijing 100142, China;
4. Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, China;
5. Key laboratory of Carcinogenesis and Translational Research(Ministry of Education), Beijing 100142, China

Received:2018-01-04 Online:2018-09-21 Published:2018-10-20
Supported by:
This study was supported by National Natural Science Foundation of China(81502578, 81872025), Beijing shijitan Hospital, Capital Medical University Youth Backbone of Subject in Training-Special Scientific Research(2016-QB11).

摘要/Abstract

摘要： 目的研究右旋葡聚糖硫酸钠（dextran sodium sulfate，DSS）诱导小鼠溃疡性结肠炎（ulcerative colitis，UC）模型引发的病理、免疫机制，以期为UC的治疗提供新的线索。方法将24只8周大的C57BL/6J清洁级子鼠分为DSS水溶液喂食1、3、5 d组以及无DSS水溶液对照组4组，每组6只。免疫组织化学检测小鼠结肠病理特征；应用实时定量聚合酶链反应（polymerase chain reaction，PCR）验证免疫因子在小鼠UC组织的表达状态。结果随着小鼠饮用DSS水溶液时间的增加，其体质量逐渐下降，结肠长度逐渐缩短，脾增大。小鼠肠黏膜组织HE染色结果显示，DSS水溶液喂食5 d组的小鼠肠黏膜有肠溃疡的症状，髓过氧化物酶（myeloperoxidase，MPO）染色可观察到中性粒细胞广泛浸润；此外，与对照组相比，炎性反应因子及炎性反应相关因子包括肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白介素-1α（interleukin-1α，IL-1α）、IL-1β、IL-6、趋化因子配体-1［chemokine （C-X-C motif） ligand 1，CXCL-1］、CXCL-2和环氧化酶-2（cyclooxygenase-2，COX-2）表达水平显著增高。结论 DSS水溶液喂食5 d可形成UC模型，并伴随炎性反应因子、趋化因子大量浸润，提示UC的发生发展与炎性反应因子浸润密切相关，可能通过抑制其免疫因子的释放而控制UC疾病的进展。

关键词: 溃疡性结肠炎, 右旋葡聚糖硫酸钠, 炎性因子, 趋化因子

Abstract: Objective To study the pathological and immune mechanism in the ulcerative colitis(UC) mice induced by dextran sodium sulfate (DSS) that could be provide clue for the treatment. Methods We feed the mice with DSS solution for one, three, five days and the solution without DSS was as control group. Immunohistochemistry was used to detect pathological feature in colon tissues of mice; real-time PCR was performed to investigate immune factors expression. Results Via DSS solution to feed the mice with a variable of times, mouse weight decreased, length of colon shortened and spleen of mice enlarged, gradually. The result from HE staining on the colon tissues of mice with 5 days DSS feeding showed that enterelcosis existed; MPO staining demonstrated that neutrophile granulocyte widely invaded. In addition, inflammatory factor and inflammatory associated factors including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6,[chemokine(C-X-C motif) ligand 1,CXCL-1], CXCL-2 and cyclooxygenase-2 (COX-2) were significantly increased. Conclusion Using DSS solution to feed the mice with 5 days formed UC model infiltrating with a lot of inflammatory factors and chemokines, indicating occurrence and progression of UC are associated with infiltrating inflammatory factors and inhibiting these factors may control disease.

Key words: ulcerative colitis, dextran sodium sulfate, inflammatory factor, chemokine

中图分类号:

R365

杨敏, 安国, 赵威, 马媛媛. 结肠炎小鼠模型的病理机制研究[J]. 首都医科大学学报, 2018, 39(5): 704-709.

Yang Min, An Guo, Zhao Wei, Ma Yuanyuan. Pathological mechanism study on the colitis mice model[J]. Journal of Capital Medical University, 2018, 39(5): 704-709.

参考文献

[1] Krugliak Cleveland N, Rubin D T, Hart J, et al. Patients with ulcerative colitis and primary sclerosing cholangitis frequently have subclinical inflammation in the proximal colon[J]. Clin Gastroenterol Hepatol,2018,16(1):68-74.
[2] Nemeth Z H, Bogdanovski D A, Barratt-Stopper P, et al. Crohn's disease and ulcerative colitis show unique cytokine profiles[J]. Cureus,2017, 9(4):e1177.
[3] 胡仁伟,欧阳钦,陈代云. 右旋葡聚糖硫酸钠小鼠溃疡性结肠炎动物模型建立方法探讨[J]. 胃肠病学,2002, 7(6):331-334.
[4] Trivedi P P, Jena G B. Dextran sulfate sodium-induced ulcerative colitis leads to increased hematopoiesis and induces both local as well as systemic genotoxicity in mice[J]. Mutat Res, 2012, 744(2):172-183.
[5] Liang J, Liang J, Hao H, et al. The extracts of morinda officinalis and its hairy roots attenuate dextran sodium sulfate-induced chronic ulcerative colitis in mice by regulating inflammation and lymphocyte apoptosis[J]. Front Immunol, 2017, 8:905.
[6] Wong W Y, Lee M M, Chan B D, et al. Proteomic profiling of dextran sulfate sodium induced acute ulcerative colitis mice serum exosomes and their immunomodulatory impact on macrophages[J]. Proteomics 2016, 16(7):1131-1145.
[7] 张忠,程富胜,贾宁,等. 小鼠溃疡性结肠炎模型的建立及病理组织学比较[J].中国实验动物学报,2012, 20(6):69-73.
[8] Zhang Z, Yang L, Wang B, et al. Protective role of liriodendrin in mice with dextran sulphate sodium-induced ulcerative colitis[J]. Int Immunopharmacol,2017, 52:203-210.
[9] Montrose D C, Horelik N A, Madigan J P,et al. Anti-inflammatory effects of freeze-dried black raspberry powder in ulcerative colitis[J]. Carcinogenesis,2011, 32(3):343-350.
[10] Sheng Y H, Lourie R, Linden S K, et al. The MUC13 cell-surface mucin protects against intestinal inflammation by inhibiting epithelial cell apoptosis[J]. Gut,2011, 60(12):1661-1670.
[11] Xu B L, Zhang G J, Ji Y B. Active components alignment of Gegenqinlian decoction protects ulcerative colitis by attenuating inflammatory and oxidative stress[J]. J Ethnopharmacol, 2015, 162:253-260.
[12] 郭瑞敏, 荀哲,范正松,等. 2,4,6-三硝基苯磺酸诱导不同鼠种急性溃疡性结肠炎的比较[J].中国医科大学学报,2016,45(9):787-792.
[13] 程慧,冯晓莹,徐华. 炎症性肠病242例临床分析[J].中国医科大学学报,2017,46(11):1039-1041.
[14] Pichai M V, Ferguson L R. Potential prospects of nanomedicine for targeted therapeutics in inflammatory bowel diseases[J]. World J Gastroenterol 2012, 18(23):2895-2901.
[15] Chintakuntlawar A V, Chodosh J. Chemokine CXCL1/KC and its receptor CXCR2 are responsible for neutrophil chemotaxis in adenoviral keratitis[J]. J Interferon Cytokine Res,2009, 29(10):657-666.
[16] Millet P, Vachharajani V, McPhail L, et al. GAPDH Binding to TNF-alpha mRNA contributes to posttranscriptional Repression in Monocytes:A Novel Mechanism of Communication between Inflammation and Metabolism[J]. J Immunol,2016, 196(6):2541-2551.
[17] Ohkusa T, Yoshida T, Sato N, et al. Commensal bacteria can enter colonic epithelial cells and induce proinflammatory cytokine secretion:a possible pathogenic mechanism of ulcerative colitis[J]. J Med Microbiol,2009, 58(Pt 5):535-545.
[18] Rachmilewitz D, Karmeli F, Shteingart S, et al. Immunostimulatory oligonucleotides inhibit colonic proinflammatory cytokine production in ulcerative colitis[J]. Inflamm Bowel Dis, 2006, 12(5):339-345.
[19] Rashidian A, Muhammadnejad A, Dehpour A R, et al. Atorvastatin attenuates TNBS-induced rat colitis:the involvement of the TLR4/NF-kB signaling pathway[J]. Inflammopharmacology,2016, 24(2-3):109-118.
[20] Yu L, Yan J, Sun Z. D-limonene exhibits anti-inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-2, PGE2 and ERK signaling pathways[J]. Mol Med Rep,2017, 15(4):2339-2346.

结肠炎小鼠模型的病理机制研究

Pathological mechanism study on the colitis mice model

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 12

编辑推荐

Metrics

本文评价

[1]	李琼, 赵建华, 刘昊, 王凡, 李青, 陈希妍, 蔡瑞艳, 吴清武, 张健, 吉四辈, 路承彪, 李少敏. 脑白质高信号患者血清CX3CL1水平与认知功能障碍的关系[J]. 首都医科大学学报, 2023, 44(1): 6-12.
[2]	张兴华, 邢洁, 孙灿, 张希, 王拥军. 溃疡性结肠炎中B细胞对巨噬细胞趋化作用的初步研究[J]. 首都医科大学学报, 2022, 43(1): 42-46.
[3]	吴慧博, 赵海英, 朱圣韬, 吴咏冬, 张澍田. 不同营养素对活动期溃疡性结肠炎患者肠道生物屏障的影响[J]. 首都医科大学学报, 2019, 40(4): 635-639.
[4]	刘国青, 陈振萍, 唐凌, 吴心怡, 甄英姿, 李刚, 王岩, 张宁宁, 张纪水, 于国霞, 吴润晖. 重型血友病A患儿关节出血后IL-1β、IL-6、TNF-α释放与关节病变形成的相关性研究[J]. 首都医科大学学报, 2018, 39(3): 314-319.
[5]	王翼飞, 麻微微, 张淑华, 何电, 余焕玲, 肖荣. 三种膳食油脂对人血清补体、细胞炎性反应因子和趋化因子及其相关蛋白水平的调节作用及机制初探[J]. 首都医科大学学报, 2018, 39(2): 252-257.
[6]	平浩, 牛亦农, 杨飞亚, 王明帅, 邢念增. CXCR4及NDRG1蛋白在前列腺癌中的表达及其与侵袭转移的相关性分析[J]. 首都医科大学学报, 2016, 37(3): 327-330.
[7]	李颖, 王向东, 王鸿, 伯铭羽, 宋贝贝, 范尔钟, 张罗. CC类趋化因子在慢性鼻窦炎的表达[J]. 首都医科大学学报, 2013, 34(6): 795-798.
[8]	何秀娟, 林燕, 吕喆, 安云庆, 丁跃中, 李萍. 朱红膏对脂多糖刺激人单核细胞系THP-1细胞分泌细胞因子和黏附分子的影响[J]. 首都医科大学学报, 2013, 34(4): 572-575.
[9]	王克迪;刘志忠;王瑞珉;康熙雄. 血清CXCL16浓度与脑卒中患者颈动脉粥样硬化的相关性研究[J]. 首都医科大学学报, 2012, 33(2): 139-142.
[10]	刘崇东;鲁琦;张震宇;邓海腾. 用蛋白质组学方法分析先兆子痫孕妇血清差异蛋白表达和急性反应蛋白[J]. 首都医科大学学报, 2012, 33(1): 20-25.
[11]	张艳丽;贾红侠;何焱玲. 趋化因子在银屑病发病机制中的作用[J]. 首都医科大学学报, 2010, 31(5): 673-677.
[12]	林栋栋;孙家邦;李非;张淑文;崔叶青;刘大川;朱斌;孙海晨;刘爽. 趋化因子CINC在急性胰腺炎大鼠肺组织中的表达[J]. 首都医科大学学报, 2005, 26(6): 737-740.