癌变·畸变·突变 ›› 2009, Vol. 21 ›› Issue (1): 10-014.doi: 10.3969/j.issn.1004-616x.2009.01.003

• 论著 • 上一篇    下一篇

肝细胞癌变过程中缺氧诱导因子-1α的动态表达与改变特征

邱历伟,姚登福,姜 华,李月明,赛文莉,袁菊萍,吴 玮,吴信华   

  1. 南通大学附属医院临床医学研究中心,江苏 南通 226001
  • 收稿日期:2008-08-27 修回日期:2008-10-08 出版日期:2009-01-30 发布日期:2009-01-30

Expression and Changes of Hepatic Hypoxia Inducible Factor-1 during the Development of Hepatocellular Carcinoma

QIU Li-wei, YAO Deng-fu, JIANG Hua, LI Yue-ming, SAI Wen-li, YUAN Ju-ping, WU Wei, WU Xin-hua   

  1. Research Center of Clinical Medicine,Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China
  • Received:2008-08-27 Revised:2008-10-08 Online:2009-01-30 Published:2009-01-30

摘要: 背景与目的: 观察肝细胞癌变过程中缺氧诱导因子-1α(HIF-1α)的动态改变及其与病理学特征的关系。 材料与方法: 以含0.05% 2-乙酰氨基芴(2-FAA)颗粒饲料连续喂饲雄性SD大鼠12周诱发肝细胞癌变,同时设正常对照组普通颗粒饲料喂饲,采用HE染色观察肝细胞形态学改变,采用酶联免疫吸附法(ELISA)检测肝细胞及外周血中HIF-1α的动态变化,并以免疫组织化学法检测肝组织HIF-1α的表达及胞内定位。 结果: SD大鼠在喂饲2-FAA后,肝细胞出现颗粒样变性、不典型增生及肝细胞癌(HCC)的变化;HIF-1α随着上述病理组织学的改变依次呈梯度增高表达,表现为肝癌组明显高于对照组和变性组(P<0.05);HIF-1α在肝细胞内呈强阳性表达;外周血与肝组织中的HIF-1α动态改变呈正相关关系(r=0.474,P<0.05)。 结论: HIF-1α参与肝细胞的癌变过程,其表达增加有助于肝癌早期诊断及预后判断。

关键词: 肝细胞癌, HIF-1α, 免疫组织化学, 癌变

Abstract: BACKGROUND AND AIM: To investigate the expression and alterations of hypoxia inducible factor-1α (HIF-1α) during development of hepatocellular carcinoma(HCC). MATERIALS AND METHODS: Rat hepatoma model was established with 2-fluorenylacetamide (2-FAA) containing-feeds for 12 weeks in male Sprague-Dawley (SD) rats. Morphological changes in rat livers were examined by HE staining. The changes of HIF-1α in rat livers and sera were quantitatively analyzed by enzyme linked immunosorbent assay (ELISA). Simultaneously, the expression and cellular distribution of liver HIF-1α were assessed by immunohistochemistry. RESULTS: Rat hepatocytes showed granule-like degeneration to atypical hyperplasia and HCC development after ingestion of 2-FAA, with progressive increase of hepatic HIF-1α expression during the course. The levels of HIF-1α in hepatoma tissues and sera were significantly higher than those in normal and degenerative tissues. Immunohistochemistry evidence showed positive expression and hepatocyte distribution of HIF-1α in rat hepatoma. A positive relationship of HIF-1α level in hepatoma tissues and sera was found(r=0.474,P<0.05). CONCLUSION: Hepatic HIF-1α may participate in hepatocytic malignant transformation. Detection of HIF-1α expression during HCC development could be a useful molecular marker for early diagnosis and prognosis of HCC.

Key words: hepatocellular carcinoma, HIF-1α, immunohistochemistry, malignant transformation