IL-17抗体灌注抑制小鼠溃疡性结肠炎相关大肠癌的发生
发布时间：2018-08-05 14:12
【摘要】：目的 应用葡聚糖硫酸钠（Dextran sulfate sodium DSS）联合二甲肼（1,2-Dimethylhydrazine DMH）建立溃疡性结肠炎相关大肠癌小鼠模型，探讨IL-17A在肿瘤发生中的作用，并观察IL-17A抗体灌注抑制炎症相关大肠癌发生的效应，为寻找治疗溃疡性结肠炎相关性大肠癌新靶点提供理论基础和尝试。 方法和材料 组A26只3周龄雄性ICR小鼠随机分成4笼（6-7只/笼）。每周给予25mg/kgDMH腹腔注射，自由饮用1%DSS溶液7天后改为普通饮用水连饮7天，，如此为一个循环；于实验13周、16周、18周和22周分别处死1笼，记录各期病变情况，运用Western Blotting检测各期结直肠组织中的IL-17A表达含量，比较差异。随后组B（6只）操作如组A，实验第十周开始隔天给与100μg/只抗IL-17A抗体腹腔注射，共注射6次；组C（5只）每周25mg/kg生理盐水腹腔注射，连续饮用普通饮用水。实验13周处死组B、组C全部小鼠；检测IL-17A含量，比较各组临床症状、肿瘤病理情况如肿瘤数目、直径大小等情况。 结果 根据蛋白条带亮度和宽度判断各组织中IL-17A含量多少，组A各期蛋白表达含量从13周到22周逐渐上升。组A各期肿瘤平均个数分别为3.50±2.16、6.43±4.72、15.17±8.06、31.40±10.78，呈上升趋势。组B蛋白条带宽度小于组A13周，肿瘤平均个数为0.60±0.89，组B组A（P0.05）。 结论 1.应用DMH联合DSS可成功诱导小鼠溃疡性结肠炎相关性大肠癌小鼠模型，为该领域的实验研究提供了重要的动物模型。 2. IL-17A在该模型中高度表达，且随时间呈逐级上升（setup）趋势，表达水平与疾病严重程度呈正相关，与预后呈负相关。 3.抗IL-17A抗体可有效中和组织中IL-17A含量，减缓病程进展，为研究该病的发生机制及探讨可能的治疗方向寻找新靶点。
[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 卤2.16, 6.43 卤4.72, 15.17 卤8.06, 31.40 卤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 卤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.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R574.62;R735.34
本文编号：2166034
[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 卤2.16, 6.43 卤4.72, 15.17 卤8.06, 31.40 卤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 卤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.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R574.62;R735.34
【参考文献】
相关期刊论文 前2条
1 万德森;结直肠癌临床研究进展[J];广东医学;2001年07期
2 ;Clinical phenotype and prevalence of hereditary nonpolyposis colorectal cancer syndrome in Chinese population[J];World Journal of Gastroenterology;2005年10期
本文编号：2166034
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