生长抑素、环氧合酶-2在肝癌发生发展中的变化及意义  

The Expressions of Somatostatin and Cycloxygenase-2 in Chronic Hepatitis,Hepatic Cirrhosis,Precancerous Lesion and Hepatocellular Carcinoma

作　　者：谢咏梅[1] 李肖[2] 严律南[3] 魏兵[4] 王春辉[2] 唐承薇[2] 

机构地区：[1]四川大学华西第二医院神经消化科,成都610041 [2]四川大学华西医院消化科,成都610041 [3]四川大学华西医院肝胆外科,成都610041 [4]四川大学华西医院病理科,成都610041

出　　处：《四川大学学报（医学版）》2015年第5期710-716,共7页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.30330270)资助

摘　　要：目的 探讨在肝癌发生发展过程中,生长抑素及其受体（SST/SSTR）和环氧合酶-2（COX-2）的表达演变规律,并分析门脉高压与SST/SSTR表达之间的关联性。方法 收集一系列肝脏手术标本：正常肝脏5例、慢性肝炎14例、肝硬化40例、癌前病变40例及肝癌组织40例,收集肝硬化经颈静脉肝内门体分流手术（TIPS）患者术前及术后外周血标本各20例。免疫组化法及RT-PCR法分别检测肝组织中SSTR 1~5亚型的蛋白及mRNA表达情况。放射免疫法检测外周血及肝组织中SST表达量。Western blot检测肝组织中COX-2蛋白表达量。结果约90%的癌前病变高表达SSTR 2、5,且SSTR表达分布呈包绕门静脉特征。至少约60%的肝癌组织表达SSTR 2、5亚型。SSTR 1~5表达量与SST表达量呈正相关。肝硬化患者TIPS术后,外周血SST水平较术前升高（P〈0.05）。COX-2在肝硬化组织中表达量最高（约90%）,在癌前病变（约80%）及肝癌中表达量降低。结论就分子靶点分布情况而言,癌前病变期可能为生长抑素类似物与COX-2抑制剂联合用药的最佳时期。而对肝癌组织,缓解门脉高压可能有利于诱导增强SSTR在肿瘤组织中的表达。Objective To investigate the expression difference of somatostatin （SST）, SST receptors （SSTR） and COX-2 in chronic hepatitis, hepatic cirrhosis, precancerous lesion and hepatocellular Carcinoma, and explore the relationship between portal hypertension and SST/SSTR expressions. Methods A series of human liver tissues were obtained from surgery, including normal liver 4 cases, chronic hepatitis 14 cases, hepatic cirrhosis 40 cases, precancerous lesion 40 cases and HCC tissues 40 cases. Peripheral bloods were collected from 20 patients before and after the operation of transjugular intrahepatic portosystemic shunt （TIPS）. SSTR 1-5 subtypes in hepatic tissues were detected by immunohistochemical study and RT-PCR. Levels of SST and COX-2 were quantified by radioimmunoassay and Western blot. Results 90% of precancerosis expressed high levels of SSTR 2,5 subtypes, and SSTR mainly distributed surrounding portal vein. At lest 60% of HCC expressed SSTR 2,5 subtypes, and there were positive correlations between levels of SSTR 1-5 and SST. Levels of SST in peripheral blood of cirrhotic patients significantly increased after TIPS（P〈0.05）. Levels of COX-2 were highest in cirrhosis （about 90 %）, and decreased in precancerosis （about 80%） and HCC tissues. Conclusions Precancerosis or early stage of HCC may be the optimum time for synergetic medication of SST analogue and COX-2 inhibitor.

关 键 词：肝细胞癌 生长抑素 环氧合酶-2 门静脉高压 

分 类 号：R735.7[医药卫生—肿瘤]