基于糖尿病-肿瘤小鼠模型研究糖尿病对结直肠癌/乳腺癌进展及肠道菌群的影响

doi:10.12300/j.issn.1674-5817.2021.066

实验动物与比较医学 ›› 2021, Vol. 41 ›› Issue (6): 469-479.DOI: 10.12300/j.issn.1674-5817.2021.066

• 人类疾病动物模型专题 • 下一篇

基于糖尿病-肿瘤小鼠模型研究糖尿病对结直肠癌/乳腺癌进展及肠道菌群的影响

王晓钰, 蒋升瑶, 蔺智兵, 崔立

上海交通大学农业与生物学院, 上海市兽医生物技术重点实验室, 上海 200240

收稿日期:2021-03-30 修回日期:2021-07-19 出版日期:2021-12-25 发布日期:2021-12-29
作者简介:王晓钰(1996—), 女, 硕士, 研究方向: 动物疾病对肠道菌群的影响。E-mail: haileyxywang@sjtu.edu.cn
崔立,上海交通大学农业与生物学院动物科学系研究员、博士生导师、人兽共患病与比较医学团队带头人。研究涉及肠道微生物与宿主互作、病毒宏基因组学,近年主要关注疾病动物模型、肠类器官模型构建,以及通过动物疾病模型和类器官探究黏膜损伤修复机制及黏膜修复活性物质评估。同时担任上海交通大学实验动物伦理委员会委员,中国畜牧兽医学会公共卫生分会理事,《中国实验动物学报》《中国比较医学杂志》《亚洲兽医案例分析》等杂志编委,英国皇家兽医学院访问学者。主持完成国家级及上海市科研项目10余项,主编上海及国家职业培训系列教材《宠物健康护理员》,发表SCI等论文45篇,获得授权专利8项。
基金资助:
交通大学-蜂妮医药合作项目(19H100000558)

Effects of Diabetes on Colorectal Cancer/Breast Cancer Progression and Intestinal Flora Based on a Diabetes-tumor Mouse Model

WANG Xiaoyu, JIANG Shengyao, LIN Zhibing, CUI Li

Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China

Received:2021-03-30 Revised:2021-07-19 Online:2021-12-25 Published:2021-12-29

摘要/Abstract

摘要： 目的通过构建糖尿病-肿瘤小鼠模型,对不同处理组小鼠体质量、肿瘤体积、生存率,以及肠道菌群数据进行统计分析,探讨糖尿病对肿瘤进展的影响,以及糖尿病合并结直肠癌或乳腺癌对肠道菌群的影响。方法 60只小鼠分为空白对照组、糖尿病组、结直肠癌组、乳腺癌组、糖尿病+结直肠癌组、糖尿病+乳腺癌组。通过链脲佐菌素注射建立糖尿病小鼠模型,在此基础上进一步建立结直肠癌和乳腺癌的实体瘤模型。观察记录各组小鼠的体质量、肿瘤体积变化,计算生存率。采集小鼠粪便,然后利用QIIME2平台基于DATA2和Vesearch方法对粪便中微生物群落测序数据进行分析。结果糖尿病合并结直肠癌或者乳腺癌后,小鼠体质量（P<0.05）和生存率（P<0.01）均明显降低,但小鼠肿瘤体积无明显变化。与空白对照组、糖尿病组或结直肠癌组相比,糖尿病+结直肠癌组小鼠肠道菌群的alpha多样性明显改变（P<0.05）,而糖尿病合并乳腺癌并未引起肠道菌群的alpha多样性产生变化（P>0.05）;同时,糖尿病合并结直肠癌或乳腺癌对小鼠肠道菌群的beta多样性和细菌物种组成也产生一定影响。结论糖尿病会促进结直肠癌或乳腺癌的进展。糖尿病合并结直肠癌或乳腺癌对小鼠肠道菌群的影响比单独结直肠癌或单独乳腺癌的影响更大。

关键词: 2型糖尿病, 结直肠癌, 乳腺癌, 肠道菌群, 小鼠

Abstract: Objective To investigate the effects of diabetes on tumor progression, and the effects of diabetes combined with colorectal or breast cancer on the intestinal flora by constructing a diabetes-tumor mouse model, and the differences in body mass, tumor volume, survival rate, and initial flora of the mice in different treatment groups were statistically analyzed. Methods Sixty mice were divided into control, diabetes, colorectal cancer, diabetes + colorectal cancer, breast cancer, and diabetes + breast cancer groups. The diabetic mouse model was established by streptozotocin injection, and solid tumor models of colorectal and breast cancer were further established on this basis. Changes in the body mass, tumor volume, and survival rate of the mice in each group were observed and analyzed. The mouse feces were collected, and then the microbial community sequencing data were analyzed using the QIIME2 platform based on the DATA2 and Vesearch methods. Results The body mass (P < 0.05) and survival rate (P < 0.01) of mice with diabetes combined with colorectal or breast cancer were significantly reduced, but there was no significant difference in tumor volume in mice. Compared with the control group or the colorectal cancer group, the species richness of the intestinal flora in mice in the diabetes + colorectal cancer group was significantly altered (P < 0.05); while the diabetes + breast cancer group did not significantly change (P > 0.05). The beta diversity and bacterial species composition of the intestinal flora in mice with diabetes combined with colorectal or breast cancer were also affected. Conclusion Diabetes promotes the progression of colorectal or breast cancer. Diabetes combined with colorectal or breast cancer has a greater impact on the intestinal flora of mice than colorectal or breast cancer alone.

Key words: Type 2 diabetes, Colorectal cancer, Breast cancer, Intestinal flora, Mice

中图分类号:

R-332
Q95-33

王晓钰, 蒋升瑶, 蔺智兵, 崔立. 基于糖尿病-肿瘤小鼠模型研究糖尿病对结直肠癌/乳腺癌进展及肠道菌群的影响[J]. 实验动物与比较医学, 2021, 41(6): 469-479.

WANG Xiaoyu, JIANG Shengyao, LIN Zhibing, CUI Li. Effects of Diabetes on Colorectal Cancer/Breast Cancer Progression and Intestinal Flora Based on a Diabetes-tumor Mouse Model[J]. Laboratory Animal and Comparative Medicine, 2021, 41(6): 469-479.

图/表 6

参考文献

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基于糖尿病-肿瘤小鼠模型研究糖尿病对结直肠癌/乳腺癌进展及肠道菌群的影响

Effects of Diabetes on Colorectal Cancer/Breast Cancer Progression and Intestinal Flora Based on a Diabetes-tumor Mouse Model

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