乙型肝炎病毒包膜转基因小鼠肝肿瘤胰岛素样生长因子Ⅰ及其受体表达的研究

Expression of Insulin-like Growth FactorⅠ and its Receptor in Liver Neoplasms of Hepatitis B Virus Transgenic Mice

研究乙型肝炎病毒（ＨＢＶ）包膜转基因小鼠肝肿瘤细胞胰岛素样生长因子Ｉ（ＩＧＦ－Ｉ）及其受体（ＩＧＦ－ＩＲ）的表达，观察ＨＢＶ包膜转基因产物在肝细胞中的定位。方法：应用原位杂交技术检测２５只肝肿瘤和１０只正常小鼠肝ＩＧＦ－ＩｍＲＮＡ和ＩＧＦ－ＩＲ ｍＲＮＡ的表达，用免疫组化法检测ＨＢＶ包膜转基因产物的表达。结果：５２％（１３／２５）的肝腺瘤ＩＧＦ－ＩＲ ｍＲＮＡ表达增高，肝肿瘤区ＩＧＦ－ＩｍＲＮＡ表达减少。正常肝有ＩＧＦ－ＩｍＲＮＡ表达，但无ＩＧＦ－ＩＲｍＲＮＡ。ＨＢＶ转基因产物主要在肝腺瘤周围的肝细胞浆内表达，在肝腺瘤内的表达显著降低。结论：ＨＢＶ转基因小鼠肝肿瘤出现ＩＧＦ－Ｉ及ＩＧＦ－ＩＲ的异常表达，可能与肝肿瘤的发生、发展过程密切相关。

Background/Aims: To investigate the expression of insulin-like growth factor Ⅰ (IGF-Ⅰ), its receptor (IGF-IR), and localization of hepatitis B virus (HBV) large envelope transgenic product in mice hepatocytes. Methods: The expressions of IGF-Ⅰ mRNA and IGF- IRmRNA were detected in hepatocellular adenomas in 25 HBV transgenic mice and in 10 normal mice livers by in situ hybridization. Localization of HBV large envelope polypeptide was detected by immunohistochemical staining. Results: The overexpression of IGF-ⅠR mRNA was shown in 13 of 25 (52%) transgenic mice with hepatic adenomas, but IGF-Ⅰ mRNA was consistently reduced except in the surrounding hepato- cytes. IGF-I mRNA was observed in normal liver tissue, but not was IGF- IR mRNA. Overproduction of the HBV large envelope was found in hepatocytic cytoplasm, but a marked reduction in expression of the large envelope polypeptide was found in the neoplastic nodules. Conclusions: The abnormal expression of IGF and its receptor appeared in adenoma of HBV transgenic mice may be involved in the development of liver neoplasm.