大肠炎促进大肠癌发生发展的实验研究

Experimental study of colitis-promoted colorectal tumorigenesis

目的通过建立小鼠结肠炎相关大肠癌模型,证实炎症加速大肠癌发生过程。方法联合或单独使用AOM致癌剂腹腔注射与DSS致肠炎药物自由饮用建立小鼠大肠炎症-癌症模型,实验共分为4组:大肠炎-癌症模型组(AOM/DSS组),单纯高剂量致癌剂-癌前病变模型组(AOM组),大肠炎症模型组(DSS组)及对照组。进行大体与病理组织学评估。结果 AOM/DSS组小鼠远端肠黏膜在4周时除表现为急性黏膜炎症外,还出现了肠隐窝病变(ACF),7周为腺瘤中-重度不典型增生改变,100天时80%的小鼠出现典型的腺癌特征。AOM组于4周时尚未见到异常组织学改变,7周时可见到ACF灶,100天时可见腺瘤样突起,灶性中-重度不典型增生。DSS组可见由急性肠黏膜炎症向慢性炎症的转化过程。结论炎症性肠癌发生的过程与散发性大肠癌的成癌过程一致,即ACF-腺瘤-腺癌三个疾病过程;炎症损伤可加速小鼠大肠癌疾病过程。

Objective To reconfirm that inflammation accelerating coloreetal tumorigenesis process by establishing colitis-associated cancer model with mice. Methods First, the colitisassociated cancer model was established by AOM intraperitoneal injection （i. p. ） and drinking water with DSS. The mice were devided into four groups： colitis-associated colon cancer group （AOM/DSS group）, high dose of carcinogen alone and precancerosis group （AOM group）, colitis group （ DSS group） and the control group. Pathologic histology of the four groups was assessed. Results Compared with the pathological characteristics of week 4, week 7, and day 100, mice in AOM/DSS group appeared acute inflammation and aberrant crypt loci （ACF） at week 4, adenoma and dysplasia at week 7 and about 80% mice with adenocarcinoma at day 100. No obviously abnormal appearance was found at week 4, ACF showed at week 7 and focal moderate to severe atypical dysplasia displayed at day 100 in AOM group. While, from acute to chronic inflammatory changes were showed in DSS group. Conclusion The process of colitis associated colon cancer is consistent with the carcinogenesis of sporatic colorectal cancer, that is ACF-adenoma-adenocarcinoma. Inflammation can really accelerate eolorectal tumorigenesis.