【摘要】：目的 應用葡聚糖硫酸鈉（Dextran sulfate sodium DSS）聯(lián)合二甲肼（1,2-Dimethylhydrazine DMH）建立潰瘍性結腸炎相關大腸癌小鼠模型，探討IL-17A在腫瘤發(fā)生中的作用，并觀察IL-17A抗體灌注抑制炎癥相關大腸癌發(fā)生的效應，為尋找治療潰瘍性結腸炎相關性大腸癌新靶點提供理論基礎和嘗試。 方法和材料 組A26只3周齡雄性ICR小鼠隨機分成4籠（6-7只/籠）。每周給予25mg/kgDMH腹腔注射，自由飲用1%DSS溶液7天后改為普通飲用水連飲7天，，如此為一個循環(huán)；于實驗13周、16周、18周和22周分別處死1籠，記錄各期病變情況，運用Western Blotting檢測各期結直腸組織中的IL-17A表達含量，比較差異。隨后組B（6只）操作如組A，實驗第十周開始隔天給與100μg/只抗IL-17A抗體腹腔注射，共注射6次；組C（5只）每周25mg/kg生理鹽水腹腔注射，連續(xù)飲用普通飲用水。實驗13周處死組B、組C全部小鼠；檢測IL-17A含量，比較各組臨床癥狀、腫瘤病理情況如腫瘤數(shù)目、直徑大小等情況。 結果 根據蛋白條帶亮度和寬度判斷各組織中IL-17A含量多少，組A各期蛋白表達含量從13周到22周逐漸上升。組A各期腫瘤平均個數(shù)分別為3.50±2.16、6.43±4.72、15.17±8.06、31.40±10.78，呈上升趨勢。組B蛋白條帶寬度小于組A13周，腫瘤平均個數(shù)為0.60±0.89，組B組A（P0.05）。 結論 1.應用DMH聯(lián)合DSS可成功誘導小鼠潰瘍性結腸炎相關性大腸癌小鼠模型，為該領域的實驗研究提供了重要的動物模型。 2. IL-17A在該模型中高度表達，且隨時間呈逐級上升（setup）趨勢，表達水平與疾病嚴重程度呈正相關，與預后呈負相關。 3.抗IL-17A抗體可有效中和組織中IL-17A含量，減緩病程進展，為研究該病的發(fā)生機制及探討可能的治療方向尋找新靶點。
[Abstract]:Objective to establish a mouse model of colorectal cancer associated with ulcerative colitis with sodium dextran sulfate (Dextran sulfate sodium DSS) combined with dimethylhydrazine (DMH), and to explore the role of IL-17A in carcinogenesis. The effects of IL-17A antibody perfusion on the occurrence of inflammatory associated colorectal cancer were observed, which provided a theoretical basis for finding new targets for the treatment of ulcerative colitis associated colorectal cancer. Methods A 26 male ICR mice aged 3 weeks were randomly divided into 4 cages (6 to 7 cages). 25mg/kgDMH was injected intraperitoneally every week. After 7 days of free drinking of 1%DSS solution, it became a cycle of drinking ordinary drinking water for 7 days, and was executed at 13 weeks, 16 weeks, 18 weeks and 22 weeks, respectively, to record the pathological changes of each stage. Western Blotting was used to detect the expression of IL-17A in colorectal tissues. Then group B (6 rats) were given intraperitoneal injection of 100 渭 g / IL-17A antibody every other day for 6 times, and group C (5 rats) received intraperitoneal injection of 25mg/kg saline every week to drink drinking water continuously. All the Band C mice were killed at the 13th week of the experiment, the content of IL-17A was detected, and the clinical symptoms, tumor pathological conditions such as tumor number, diameter and so on were compared. Results according to the brightness and width of protein bands, the content of IL-17A in each tissue was determined, and the protein expression in group A increased gradually from 13 weeks to 22 weeks. The average number of tumors in each stage of group A was 3.50 鹵2.16, 6.43 鹵4.72, 15.17 鹵8.06, 31.40 鹵10.78, which showed an upward trend. The width of group B protein band was smaller than that of group A 13 weeks, the average number of tumor was 0.60 鹵0.89, group B group A (P0.05). Conclusion 1. The mouse model of ulcerative colitis associated colorectal carcinoma can be successfully induced by DMH combined with DSS, which provides an important animal model for the experimental research in this field. 2. The expression of IL-17A was highly expressed in the model, and the expression level of (setup) increased gradually with time. The expression level was positively correlated with the severity of the disease and negatively correlated with the prognosis. Anti IL-17A antibody can effectively neutralize the content of IL-17A in tissues and slow down the progression of the disease. It is a new target to study the pathogenesis of the disease and to explore the possible therapeutic direction.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R574.62;R735.34

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本文編號：2166034