肝纤维化对结肠癌肝转移的影响及TIMP-1、CTGF在其过程中的机制研究  

The effect of hepatic fibrosis inhibiting liver metastasis of colon cancer and the roles of TIMP - 1 and CTGF in the process

作　　者：孟磊[1] 张丽[2] 李潜[1] 夏鹏[1] 

机构地区：[1]西安交通大学医学院第一附属医院肿瘤外科,陕西西安710061 [2]西安交通大学医学院第一附属医院门诊部,陕西西安710061

出　　处：《现代肿瘤医学》2013年第9期1937-1941,共5页Journal of Modern Oncology

基　　金：陕西省社会发展公关计划项目(编号:S2011SF1851);西安市科技计划社会发展研发项目(编号:SF1021)

摘　　要：目的:通过建立小鼠肝纤维化模型及肝纤维化基础上的结肠癌肝转移模型,阐明肝纤维化对肝转移癌发生的影响,探讨TIMP-1、CTGF在肝纤维化抑制结肠癌肝转移中的作用。方法:BALB/c小鼠76只,随机分为A、B两组,A组为正常对照组,B组采用CCl4灌胃法构建肝纤维化模型。病理切片证实肝纤维化模型制作成功后,将B组随机分为B1和B2两组,A组同时随机分为A1和A2两组,每组均为19只。取A2和B2组,将培养好的小鼠结肠癌CT26细胞应用脾脏种植切除脾脏法构建结肠癌肝转移模型。2周后处死各组动物,比较A2和B2组小鼠肝转移率,并采用免疫组化方法对TIMP-1、CTGF在各组肝脏中的表达进行分析。结果:动物模型构建成功,病理切片证实肝纤维化及肝转移癌的发生。A2组肝转移发生率为82.4%(14/17),B2组肝转移发生率为25%(4/16),差异有统计学意义(P<0.05)。TIMP-1、CTGF在B1、B2组肝脏的表达与A1、A2组相比均升高,差异有统计学意义(P<0.05)。结论:肝纤维化对肝转移癌的发生有抑制作用。TIMP-1、CTGF可能在肝纤维化抑制结肠癌肝转移中发挥作用。Objective：To establish mice model of liver metastasis of colon cancer on the basis of hepatic fibrosis,and study the effect of hepatic fibrosis on liver metastasis.Using immunohistochemical method to analize the expression of TIMP-1 and CTGF in each group,and the roles of TIMP-1 and CTGF in the process of hepatic fibrosis inhibting liver metastasis of colon cancer.Methods：All 76 BALB/c mice were randomly assigned to two groups：Group A normal control group,group B constructed to hepatic fibrosis model by pouring into stomach with CCl4.Then randomly divided group A into two groups,group A1 and group A2.Group B was also divided into B1 and B2.Take group A2 and B2 to construct models of liver metastasis of colon cancer by injecting CT26 suspension into spleen then operating splenectomy.2 weeks later all mice were executed.Compare the different liver metastasis incidence of group A2 and B2.Using immunohistochemical method to analyze the expression of TIMP-1 and CTGF in each group,exploring the roles of TIMP-1 and CTGF in the process of hepatic fibrosis inhibting liver metastasis of colon cancer.Results：Animal models were constructed successfully.Pathological confirmed occurrence of liver fibrosis and liver metastasis.Incidence of hepatic metastases of group A2 was 82.4％ （14/17）,group B2 was 25％ （4/16） （P ＜0.05）.Comparing with group A1 and A2,expression of CTGF and TIMP-1 in liver of group B1 and B2 was higher （P ＜ 0.05）.Conclusion：Hepatic fibrosis have an inhibit effect for liver metastasis of colon cancer.TIMP-1,CTGF may play an important role in the inhibition of liver metastases from colorectal on hepatic fibrosis.

关 键 词：结肠癌 肝转移 肝纤维化 TIMP-1 CTGF 

分 类 号：R735.35[医药卫生—肿瘤]