溃疡性结肠炎及溃疡性结肠炎相关性结直肠癌小鼠模型中血管生成因子的表达及其与血管新生的关系  

Expression of Angiogenesis-related Factors in the Mouse Model of Ulcerative Colitis and Ulcerative Colitis-associated Colorectal Cancer and Their Relationships to Angiogenesis

作　　者：刘维新[1] 张绅[1] 任益[1] 桑立轩[1] 顾寿智 

机构地区：[1]中国医科大学附属第一医院消化内科,沈阳110001 [2]聖隷クリストフア一大学,日本浜松4338558

出　　处：《中国医科大学学报》2013年第3期231-234,266,共5页Journal of China Medical University

基　　金：辽宁省自然科学基金资助项目(20062098)

摘　　要：目的观察葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)及溃疡性结肠炎相关性结直肠癌(UCACRC)组织中血管生成相关因子的表达及其与血管生成的关系。方法应用DSS与水循环交替口服诱导反复发作的UC小鼠模型(n=23),1,2-二甲肼(DMH)/DSS联合法建立UCACRC小鼠模型(n=23),同时设立对照组(n=20)。分时段处死小鼠,观察其结肠组织的改变,用S-P免疫组化法检测3组小鼠的UC组织、UCACRC组织及正常结肠组织中血管生成素(Ang-2)、缺氧诱导因子(HIF)、血管内皮生长因子(VEGF)及其受体Flk-1的表达水平。结果单纯使用DSS可建立UC小鼠模型。第9个周期末处死的小鼠中,UC组仅有15.38%(2/13)发生低度不典型增生,而加用DMH的UCACRC组不典型增生和癌变率可达92.31%(12/13)。Ang-2、HIF、VEGF、Flk-1在UC组织、UCACRC组织中呈高水平表达,其阳性率明显高于正常结肠组织(P均<0.05),且循环周期越多,表达水平越高;但UC组织和UCACRC组织比较,4种血管生成相关因子表达的差异均无统计学意义(P均>0.05)。结论 Ang-2、HIF、VEGF、Flk-1在UC及UCACRC的血管生成过程中起着重要的作用,与炎症及肿瘤的发生、发展密切相关。Objective To observe the expression of angiogenesis-related factors in the tissues of the dextran sodium sulfate （DSS）-induced ulcerative colitis （UC） and 1,2-dimethylhydrazine （DMH）/DSS-indueed ulcerative colitis associated eolorectal cancer （UCACRC）,and to explore the relationship to angiogenesis. Methods UC （n =23 ） and UCACRC （n =23 ） mouse model were established using the DSS- induced method and DMH/DSS method, respectively. Meanwhile, a control group was set up with 20 mice. Mice in different groups were sac- rificed at different time points to determine the changes of the colon tissues. The expressions of the Ang-2, HIF,VEGF and Flk-1 in the UC tissue, UCACRC tissue and normal tissue were analyzed by S-P immunohistochemical method. Results UC mouse model can be estab- lished using DSS alone;however,the incidence rate of the low grade of atypical hyperplasia in the end of 9th cycle is only 15.38% （2/13）, which was 92.31% （atypical hyperplasia and neoplasm. 12/13 ） in the group of the mice administrated by DHM and DSS. The expression levels of the Ang-2,HIF,VEGF and Flk-1 in the UC tissue and UCACRC tissue were much higher than those in normal tissue （P 〈 0.05）, and the expression level increased with the penod. There was no obvious difference between the UC tissue and UCACRC tissue （P 〉 0.05 ）. Conclusion Ang-2, HIF, VECF and Flk-1 play important roles in the process of the angiogenesis of UC and UCACRC, which are closely related to the occunrence and development of inflammation and tumorigenesis.

关 键 词：血管生成相关因子 溃疡性结肠炎 溃疡性结肠炎相关性结直肠癌 

分 类 号：R574.62[医药卫生—消化系统]