结肠炎小鼠模型的病理机制研究  

Pathological mechanism study on the colitis mice model

作　　者：杨敏 安国[2,3] 赵威 马媛媛[5,3] Yang Min;An Guo;Zhao Wei;Ma Yuanyuan(Department of Gerontology,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Department of Laboratory Animal,Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Cell Biology,Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Thoracic Surgery II,Peking University Cancer Hospital&Institute,Beijing 100142,China;Key laboratory of Carcinogenesis and Translational Research(Ministry of Education),Beijing 100142,China)

机构地区：[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]恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [4]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 [5]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

出　　处：《首都医科大学学报》2018年第5期704-709,共6页Journal of Capital Medical University

基　　金：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)~~

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(CX-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。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.

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 

分 类 号：R365[医药卫生—病理学]