溃疡性结肠炎动物模型研究进展

doi:10.12300/j.issn.1674-5817.2021.155

实验动物与比较医学 ›› 2022, Vol. 42 ›› Issue (3): 220-228.DOI: 10.12300/j.issn.1674-5817.2021.155

溃疡性结肠炎动物模型研究进展

胡宇¹(), 兰昀羲¹, 陈晓晓¹, 熊伟², 唐宋琪³, 贾波¹, 黄巍¹()()

^1.成都中医药大学, 成都 611137
^2.成都岐黄博恩生物科技有限公司, 成都 611139
^3.海南医学院, 海口 571199

收稿日期:2021-09-22 修回日期:2022-01-21 出版日期:2022-06-25 发布日期:2022-07-01
通讯作者: 黄巍（1974—），女，教授，博士研究生导师，研究方向：方剂配伍规律的研究。E-mail： gracehw@126.com。ORCID： 0000-0003-1216-5884
作者简介:胡宇（1998—），男，硕士研究生，研究方向：脾胃病证的方剂配伍理论与临证运用研究。E-mail： 2020ks035@stu.cdutcm.edu.cn
基金资助:
国家自然科学基金资助项目：基于异功散中陈皮对肠吸收动力学影响的“补而不滞”配伍机制研究(81860816┫。国家自然科学基金资助项目：逆流挽舟法调控tuft细胞促肠干细胞增殖修复溃疡性结肠炎黏膜的机制研究┣82074327)

Research Progress in Animal Models of Ulcerative Colitis

Yu HU¹(), Yunxi LAN¹, Xiaoxiao CHEN¹, Wei XIONG², Songqi TANG³, Bo JIA¹, Wei HUANG¹()()

^1.Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
^2.Chengdu Qihuang Boen Bio-technology Co. , Ltd. , Chengdu 611139, China
^3.Hainan Medical University, Haikou 571199, China

Received:2021-09-22 Revised:2022-01-21 Published:2022-06-25 Online:2022-07-01
Contact: HUANG Wei (ORCID: 0000-0003-1216-5884), E-mail: gracehw@126.com

摘要/Abstract

摘要：

作为一种炎性肠病，溃疡性结肠炎（ulcerative colitis，UC）的发病机制尚未被完全揭示，其治疗策略仍需继续探索。动物模型是疾病研究中不可或缺的工具。因此，建立与人类UC发病机制、病理表现类似的动物模型有利于对该疾病进行充分研究。本文梳理了UC动物模型的研究进展，发现化学药物诱导是迄今为止最常用的UC造模方法；基于基因组学技术的发展，基因编辑或基因敲除诱导的自发性结肠炎则是未来动物模型研究的重要方向；评价UC动物模型造模结果的指标仍需进一步探索。

关键词: 溃疡性结肠炎, 动物模型, 发病机制, 基因敲除, 评价指标

Abstract:

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease. Its pathogenesis has not been fully revealed. Moreover, the lack of effective and safe treatment strategies is an obstacle for UC treatment currently. Animal models are essential tools in disease research. Therefore, the establishment of animal models with pathological manifestations similar to human UC is conducive to the full study of this disease. In this review, we reviewed the research progress of animal models of UC, and found that chemical induction is the most commonly used method for modeling UC. Based on the development of genomics technology, gene editing or knockout-induced spontaneous colitis is a vital direction for animal models research in the future. In addition, the indexes for evaluating the modeling results of UC animal models need to be further explored.

Key words: Ulcerative colitis, Animal model, Pathogenesis, Gene knockout, Evaluation Indicators

中图分类号:

R-332

胡宇, 兰昀羲, 陈晓晓, 熊伟, 唐宋琪, 贾波, 黄巍. 溃疡性结肠炎动物模型研究进展[J]. 实验动物与比较医学, 2022, 42(3): 220-228.

Yu HU, Yunxi LAN, Xiaoxiao CHEN, Wei XIONG, Songqi TANG, Bo JIA, Wei HUANG. Research Progress in Animal Models of Ulcerative Colitis[J]. Laboratory Animal and Comparative Medicine, 2022, 42(3): 220-228.

图/表 6

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造模方式 Modeling method	动物品系 Animal	造模过程 Modeling process	采样部位 Sample site	评价指标 Evaluation index	参考文献 Reference
DSS	BALB/c、 C57BL/6、Swiss、昆明小鼠	2%~5%的DSS溶液予以小鼠自由饮用5~7 d	结肠、直肠组织	DAI评分、组织病理学改变、MPO、IFN-γ、TNF-α、IL-1β、IL-4、IL-6	[31-41]
DSS	C57BL/6小鼠	2% DSS溶液自由饮用5 d后停药14 d。给药3轮，共43 d诱导慢性UC模型	血液、结肠组织	DAI评分、组织病理学评分、IFN-γ、IL-4、IL-17	[42]
TNBS	BALB/c小鼠	5 % TNBS 150 mg/kg与乙醇溶液以4︰1的比例进行混合后灌肠	眼眶血、结肠组织	DAI评分、结肠黏膜肉眼评分、组织病理学评分、IL-6、IL-8、TNF-α	[43]
OXA	BALB/c小鼠	丙酮︰橄榄油=4︰1比例，加入200 μL 3%的噁唑酮，涂抹于小鼠背部致敏。第8天，将1%噁唑酮100 μL溶入50 %乙醇溶液，注入小鼠直肠	结肠组织	DAI评分、组织病理学评分、IFN-γ、IL-4、IL-5、IL-13、IL-17A、TGF-β1	[44]

造模方式 Modeling method	动物品系 Animal	造模过程 Modeling process	采样部位 Sample site	评价指标 Evaluation index	参考文献 Reference
DSS	BALB/c、 C57BL/6、Swiss、昆明小鼠	2%~5%的DSS溶液予以小鼠自由饮用5~7 d	结肠、直肠组织	DAI评分、组织病理学改变、MPO、IFN-γ、TNF-α、IL-1β、IL-4、IL-6	[31-41]
DSS	C57BL/6小鼠	2% DSS溶液自由饮用5 d后停药14 d。给药3轮，共43 d诱导慢性UC模型	血液、结肠组织	DAI评分、组织病理学评分、IFN-γ、IL-4、IL-17	[42]
TNBS	BALB/c小鼠	5 % TNBS 150 mg/kg与乙醇溶液以4︰1的比例进行混合后灌肠	眼眶血、结肠组织	DAI评分、结肠黏膜肉眼评分、组织病理学评分、IL-6、IL-8、TNF-α	[43]
OXA	BALB/c小鼠	丙酮︰橄榄油=4︰1比例，加入200 μL 3%的噁唑酮，涂抹于小鼠背部致敏。第8天，将1%噁唑酮100 μL溶入50 %乙醇溶液，注入小鼠直肠	结肠组织	DAI评分、组织病理学评分、IFN-γ、IL-4、IL-5、IL-13、IL-17A、TGF-β1	[44]

分值 Score	体质量 Weight	大便形状 Stool form	血便 Bloody stool
0	无下降	正常	大便隐血阴性
1	下降1%～5%	轻微软便	大便隐血阳性
2	下降6%～10%	明显软便	肉眼可见轻微便血
3	下降11%～15%	腹泻	肉眼可见明显便血
4	下降≥15%

分值 Score	体质量 Weight	大便形状 Stool form	血便 Bloody stool
0	无下降	正常	大便隐血阴性
1	下降1%～5%	轻微软便	大便隐血阳性
2	下降6%～10%	明显软便	肉眼可见轻微便血
3	下降11%～15%	腹泻	肉眼可见明显便血
4	下降≥15%

分数 Score	炎性反应程度 Inflammation level	病变深度 Lesion depth	隐窝损伤 Crypt damage	损伤范围 Lesion range
0	无炎症	无病变	无损伤	无损伤
1	轻微炎症	至黏膜层	基部1/3受损	1%～25%
2	中度炎症	至黏膜层和黏膜下层	基部2/3受损	26%～50%
3	严重炎症	穿透肠壁	仅上皮细胞完好	51%～75%
4			隐窝、上皮细胞全部丢失	76%～100%

溃疡性结肠炎动物模型研究进展

Research Progress in Animal Models of Ulcerative Colitis

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