Research Progress in Animal Models of Ulcerative Colitis

doi:10.12300/j.issn.1674-5817.2021.155

Abstract

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

CLC Number:

R-332

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.

Figures/Tables 6

References 60

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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%