经小鼠活体肠镜行肠黏膜下注射建立结直肠癌原位模型的研究  

Establishment of orthotopic colorectal cancer model by colonoscopy with submucosal injection in living mice

作　　者：吴正春[1] 王凌翔[1,2] 苗雄鹰 杨竹林[1] 陈康[1] 王昆鹏[1] 陈文浩[1] 张子建 邓凯 胡俊蛟[3] 杨西斌 文宇[1] 熊力[1,4] Wu Zhengchun;Wang Lingxiang;Miao Xiongying;Yang Zhulin;Chen Kang;Wang Kunpeng;Chen Wenhao;Zhang Zijian;Deng Kai;Hu Junjiao;Yang Xibin;Wen Yu;Xiong Li(Department of General Surgery,the Second Xiangya Hospital of Central Southern University,Changsha 410011,China;Department of General Surgery,the Central Hospital of Shaoyang,Shaoyang 422000,China;Department of Radiology,the Second Xiangya Hospital of Central Southern University,Changsha 410011,Chin;Suzhou Institute of Biomedical Engineering and Technology,Chinese Academy of Sciences,Suzhou 215163,Chin)

机构地区：[1]中南大学湘雅二医院普外科,长沙410011 [2]湖南省邵阳市中心医院普外科,422000 [3]中南大学湘雅二医院放射科,长沙410011 [4]中国科学院苏州生物医学工程技术研究所,215163

出　　处：《国际生物医学工程杂志》2018年第3期250-256,共7页International Journal of Biomedical Engineering

基　　金：国家重点研发计划（2017YFC0109900）;国家自然科学基金（81773293,81402536,31660266,61405238）;湖南省科技计划（2015GK3117,2017DK2011）

摘　　要：目的 搭建小鼠活体肠镜平台,直视下建立小鼠结直肠癌原位模型,并观察其转移等生物学行为.方法 8周龄雄性C57/BL小鼠经麻醉后,分别用自主研发活体结肠软镜及奥林巴斯URF-P5输尿管软镜观察小鼠肠腔,对比成像效果.肠镜直视下将人结肠癌HT-29细胞注射至BALB/c-nu小鼠结肠黏膜下,注射后第3、7、15天复查肠镜,观察肠腔内成瘤情况.当小鼠体质量明显下降、呈恶病质时,予处死,探查腹腔,观察腹腔内成瘤及转移情况,标本送病检.结果 自主研发搭建的小鼠活体肠镜平台可清晰观察肠腔,未致小鼠死亡.在小鼠活体肠镜直视下行肠黏膜下注射HT-29细胞,穿孔率为15％,小鼠死亡率为33.3％,成瘤率为62.5％,腹腔转移率为60％,肝脏转移率为25％,腹壁转移率为25％.结论 自主研发搭建的小鼠活体肠镜平台能用于小鼠活体结直肠研究,其成像效果不亚于奥林巴斯URF-P5输尿管软镜;此外,结合黏膜下注射技术,可建立符合结直肠癌临床病理过程的原位模型.Objective To set up a living mice colonoscopy platform to establish an orthotopic model of colorectal cancer in mice under direct vision,and to observe its biological behavior such as metastasis.Methods Eighteen-week-old male C57/BL mice were anesthetized,and the intestinal lumen of the mice was examined by a self-developed living mice colonoscopy and Olympus URF-P5 ureteroscopy,respectively.The imaging effects of the two methods were compared.Human colon cancer HT-29 cells were injected into the colonic mucosa of BALB/c-nu mice under direct vision.The colonoscopy was performed on the 3rd,7th and 15th day after the injection to observe the tumor formation in the intestinal lumen.The mice were sacrificed when the body weight decreased significantly or cachexia appeared,and then the abdominal cavity was examined including the tumor formation and metastasis.Results The self-developed living mice colonoscopy platform can provide clear vision of enteric cavity,and no mice died in the colonoscopy examination.In vivo subcutaneous injection of HT-29 cells in mice was performed with a perforation rate of 15%,a mortality rate of 33.3%,a tumor formation rate of 62.5%,an abdominal metastasis rate of 60%,a liver metastasis rate of 25%,and an abdominal wall transfer rate of 25%.Conclusion The self-developed mice colonoscopy platform can be used for the study of colorectum in living mice.The imaging effect is no less than that of Olympus URF-P5 ureteroscopy.In addition,an orthotopic colorectal cancer model can be established by this platform combing with submucosal injection technology.

关 键 词：小鼠活体肠镜 黏膜下注射 T分期 肿瘤微环境 结直肠癌原位模型 

分 类 号：R-332[医药卫生] R735.34