DMH/DSS复合法诱导小鼠溃疡性结肠炎相关癌变的实验研究

An Experimental Study on Ulcerative Colitis Related Colon-carcinogenesis Induced by Intraperitoneal Injection of DMH and Oral Administration of DSS

目的探讨DMH腹腔注射结合3%DSS自由饮用法制备溃疡性结肠炎相关癌变小鼠模型。方法适应性喂养1周后,30只BALB/c小鼠按体重随机分为4组,正常组6只,模型Ⅰ组8只,模型Ⅱ组8只,模型Ⅲ组8只。除正常组外,其余3组,分别按15,20,25 mg/kg腹腔注射0.4%DMH,每周2次,继而连续自由饮用3%DSS2周为1循环;连续3个循环。第9周末将全部小鼠脱椎处死,截取全部结肠(回盲部-肛门),肉眼及光镜下观察小鼠结肠组织形态学变化。结果模型Ⅲ组全部小鼠在造模过程中死亡。肉眼见模型Ⅰ组小鼠结肠黏膜充血水肿;模型Ⅱ组小鼠结肠散在、多处息肉状隆起变化;正常组小鼠结肠黏膜未见异常。镜下见模型Ⅰ组小鼠结肠可见腺体萎缩、低级别上皮内瘤变;模型Ⅱ组小鼠结肠可见腺体萎缩、高级别上皮内瘤变,部分癌变;正常组小鼠结肠黏膜未见异常。结论 0.4%DMH 20mg/kg腹腔注射结合3%DSS自由饮用复合法,可以成功复制溃结相关癌变模型,该方法简单易行,与人溃疡性结肠炎相关癌变较为相似,值得推广应用。

ObjectiveTo discuss the mechanism of ulcerative colitis related to cancerogenesis induced by intraperitoneal injection of DMH and oral administration of DSS.MethodsAfter one week adaptive feed,thirty BALB/c rats were divided into four groups randomly： normal group,blank groupⅠ,blank groupⅡ and blank group Ⅲ.Except normal group,the other groups were intraperitoneal injected with 0.4%DMH（15 mg/kg,20 mg/kg,25 mg/kg） for two times a week.After intraperitoneal injection of DMH,all blank groups were given orally 3% DSS for two weeks.The above process was repeated two times.At the end of the ninth week,all rats were sacrificed and the pant-colon was preserved.The colon histomorphology was assayed by naked eyes and light microscope.ResultsThe rats in blank group Ⅲ are all dead in the course of expeiment.There were hyperemia and edema in colon mucosa of blank groupⅠ and occupation changes of polyps in colon mucosa of blank groupⅡby naked eyes.However,there was no abnormal change in normal group.The intestinal gland atrophy was detected in blank groupⅠ and groupⅡ.Meanwhile,the changes of high-grade intraepithelial neoplasia and carcinogenesis were seen in groupⅡ,while there was not abnormal in normal group.ConclusionAn ulcerative colitis related colon-cancerogenesis model can be successfully induced by intraperitoneal injection of DMH and oral administration of DSS.The model is deserved to popularization and application.