炎症因子与肝癌干细胞标志在肝癌诱导过程中的相关性研究  

Correlation between inflammation factors and hepatic cancer stem cell markers during hepatocarcinogenesis

作　　者：吴林[1] 宦宏波 吴黎雳 别平[1] 夏锋[1] 

机构地区：[1]第三军医大学西南医院全军肝胆外科研究所,重庆400038

出　　处：《实用临床医药杂志》2014年第7期1-6,共6页Journal of Clinical Medicine in Practice

基　　金：国家自然科学基金资助项目(81272224)

摘　　要：目的探讨Kupffer细胞相关炎症因子在大鼠肝癌诱导过程中的动态变化与肝癌干细胞标志的相关性。方法选取雄性SD大鼠35只,分为正常对照组(n=5)和诱导模型组(n=30)。诱导模型组大鼠饮水中加入二乙基亚硝胺溶液,正常对照组给予普通饮水。在诱癌过程中每隔4周取材5只大鼠肝脏,运用免疫组化法测定Kupffer细胞ED2抗体在肝组织的表达和定量PCR方法检测肝组织中Kupffer细胞释放的炎症因子及肝癌干细胞标志物的基因表达。并采用Pearson检验分析相关炎症因子与肝癌干细胞标志物之间相关性。结果成功建立大鼠肝癌诱导模型,在24周时诱导模型组大鼠出现肝脏肿瘤;ED2抗体在诱癌过程中呈明显升高的趋势(P<0.001);PCR结果提示,Kupffer细胞分泌的相关炎症因子IL-6、MCP-1、TGF-β、TNF-α在诱癌过程中逐渐升高(P<0.05),同时,肝癌干细胞标志物CD90在诱癌过程中呈明显升高趋势(P<0.001)。Pearson相关性检验提示:IL-6、MCP-1、TGF-β的表达变化与CD90呈明显正相关(P<0.001)。结论 Kupffer细胞释放的炎症因子IL-6、MCP-1、TGF-β的表达升高与CD90上调呈明显正相关,进一步明确了Kupffer细胞促进肝癌发生的重要作用。Objective To investigate the correlation between inflammation factors of Kupffer cells and hepatic cancer stem cell markers. Methods 35 male SD rats were divided randomly into two groups ： normal group （ 5 rats） and diethylnitrosamine （DEN） -induced groups （ 30 rats）. DEN-in-duced groups were given DEN solution in drinking water, while normal group was given normal water. 5 rats of DEN-induced group were sacrificed every 4 weeks, then immunohistochemisty was taken to evaluate the ED2 expression of Kupffer cells, and the expressions of inflammation factors and hepatic cancer stem cell markers were measured by rt-PCR. Correlation between inflammation factors and he- patic cancer stem cell markers was evaluated by Pearson analysis. Results The HCC model was successfully established at 24 weeks. Expressions of ED2 gradually increased （P 〈 0. 001 ）. The rt-PCR results indicated that the expressions of IL-6, MCP-1 ,TGF-β and TNF-α gradually increased during hepatocarcinogenesis （ P 〈 0.0 5 ） , while CD_90 expressed a significant increasing in the process （ P 〈 0.00 1 ） . Pearson analysis showed CD_90 was positively correlated with IL -6, MCP - l and TGF - β （ P 〈 0. 001 ）. Conclusion There is a significant correlation between the increase expressions of IL-6, MCP-1 ,TGF-β and the up-regulation of CD_90, which can demonstrate the essential role of Kupffer cells during hepatocarcinogenesis.

关 键 词：肝癌 KUPFFER 炎症因子 肝癌干细胞标志 

分 类 号：R735.7[医药卫生—肿瘤]