葡聚糖硫酸钠和偶氮氧甲烷建立小鼠溃疡性结肠炎癌变模型

摘要

Objective To develop an ulcerative colitis-associated carcinogenesis model in mice. Methods Female B ALB/c mice were randomly divided into 4 groups: the control group, the azoxymethane (AOM) group, the dextran sulfate sodium (DSS) group and the AOM + DSS group. AOM was intraperi-toneally injected. DSS was fed for 1 week then with ordinary water for 2 weeks, such 3 weeks formed a cycle and 9 weeks in all. The body weight was detected weekly and the mental status, stool character, hairs glossy and mortality were daily observed and recorded. Levels of TNF-a was tested by ELISA. Inflammation and pathology were observed by HE staining. Results ① After drinking DSS,the mice showed diarrhea, bloody stool, weight loss, depressed and hairs messy. Post-oral tumor were seen anal prolapse. Non-DSS groups had no more performance. AOM + DSS group appeared one death. The body weight was significantly decreased at 4,7,8,9 week after treatment compared with the control group (P <0.05). ② The TNF-a was significantly increased in DSS groups (P<0.05). ③ HE staining: DSS groups showed infiltration of inflammatory cells and (or) the formation of lymphoid follicles. The tumors were induced in all of the AOM + DSS mice (9/9), which were most located in distal colon and the pathology were showed high atypical hyperplasia and (or) carcinoma in situ. Dysplasia or cancer was not observed in the other three groups. Conclusion Ulcerative colitis-associated carcinogenesis model in mice can prepared with a single intraperitoneal injection of azoxymethane prior to three repetitive oral administrations of dextran sulfate sodium. This method have the advantages with shorter time, high formation of tumor and stability of histological type.%目的 建立溃疡性结肠炎癌变的小鼠模型.方法 雌性BALB/c小鼠随机分为4组:正常对照组、偶氮氧甲烷(AOM)组、葡聚糖硫酸钠(DSS)组、AOM+DSS组,AOM一次性腹腔注射,DSS喂养1周+普通水2周,如此3个循环共9周.每周称量体重,记录精神状态、大便性状、体毛亮泽及死亡时间,9周末取血用ELISA法检测TNF-a水平,HE染色观察炎症及病理类型.结果 ①小鼠饮用DSS后可出现腹泻、血便、体重下降、精神不振、体毛凌乱等,后期可见肛口肿物脱出.AOM+DSS组第4、7、8、9周末体重较正常对照组明显下降( P<0.05); ②DSS两组血浆TNF-a水平显著升高(P<0.05); ③HE染色,DSS两组可见炎细胞浸润和(或)淋巴滤泡形成.AOM+DSS组存活小鼠全部成瘤,肿瘤多位于远段结肠,病理组织学诊断为高度不典型增生和(或) 原位癌,另3组未见不典型增生或癌变.结论 低剂量AOM一次性腹腔注射联合DSS三循环喂养可建立溃疡性结肠炎癌变模型,该方法 时间较短,成瘤率高,病理类型稳定.