利用藥物誘發小鼠大腸炎症及大腸癌之研究

Abstract

本研究使用C57BL/6JNarl雄性小鼠，由肛門灌入2或3 mg的2,4-Dinitrobenzene sulfonic acid hydrate (DNBS)，分別在3天及14天後評估大腸的發炎程度。病理結果顯示在第一次灌藥後3天可見急性大腸炎症反應，並且於某些腸道區段，有大量炎症細胞聚集及腸黏膜壞死的現象。然而在第一次灌藥後14天觀察，炎症反應便已消退，且大腸黏膜皆恢復正常。因此這一動物模式較適合用來研究大腸急性期炎症反應，而不適合做慢性炎症性腸道疾病或進一步誘發大腸癌的探討。文獻指出azoxymethane (AOM)單獨注射或倂用dextran sodium sulfate (DSS)口服可誘發小鼠大腸癌，本研究亦使用C57BL/6JNarl及BKS.Cg-+Leprdb/+Leprdb雄性小鼠，皮下注射AOM 10 mg/kg，每週1次共3次，於40週後始發現aberrant crypt foci (ACF)。另一方面，若選用BALB/cByJNarl雄性小鼠，僅1次腹腔注射相同劑量的AOM，於一週後連續給予7天1% DSS於飲水中，在22週便可觀察到ACF。這些結果顯示配合不同藥物及小鼠品系的使用，可誘發ACF來建立一個良好的動物模式供腸道疾病之研究。

The severities of colonic inflammation were assessed 3 and 14 days after rectum injection of 2,4-Dinitrobenzene sulfonic acid (DNBS) 2 or 3 mg in C57BL/6JNarl male mice. The pathological results showed DNBS produced acute colitis 3 days after first administration with inflammatory cells aggregation and mucosa necrosis, especially in certain sections of colon. However, on day 14, the inflammation had subsided and the mucosa was recovered to normal. Therefore, this animal model is suitable for the study of acute colitis than chronic colitis or further colorectal cancer research. Previous studies showed that injection of azoxymethane (AOM) alone or with oral exposure to dextran sodium sulfate (DSS) could induce mouse colorectal cancer. In this study, C57BL/6JNarl and BKS.Cg-+Leprdb/+Leprdb male mice were treated subcutaneous with AOM 10 mg/kg once a week for 3 weeks. The aberrant crypt foci (ACF) can only be observed after 40 weeks. On the other hand, BALB/cByJNarl mice were given a single intraperitoneal injection of AOM, followed by 1% DSS in drinking water for 7 days, ACF can be observed after 22 weeks. These results indicated that drugs and mouse strains coordination should be considered for ACF induction in the establishment of intestinal disease mouse model.