实验性肝细胞癌变过程中嗜碱性小细胞病灶的癌变趋势  

Malignant tendency of basophilic liver cells in experimental rat hepatocarcinogenesis

作　　者：王晓明[1] 王宝恩[1] 王泰龄[2] 欧晓娟[1] 尤红[1] 马红[1] 贾继东[1] 

机构地区：[1]首都医科大学附属北京友谊医院肝病中心,北京100050 [2]中日友好医院病理科

出　　处：《中华肝脏病杂志》2006年第7期495-498,共4页Chinese Journal of Hepatology

基　　金：北京市科委资助项目(H020920020730)

摘　　要：目的动态观察肝癌的发生、发展过程,探讨肝细胞癌前期病变的形态特点及其癌变过程。方法145只雄性SD大鼠随机分成模型组和正常对照组,模型组大鼠以质量体积分数为1％的二乙基亚硝胺60 mg／kg灌胃,每周1次, 第12周后改为40mg／kg至14周后停药;正常对照以等渗盐水灌胃。于实验开始后第2、3、5、8、10、12、14、18周分批处死大鼠．剩余大鼠第26周全部处死。肝组织苏木精-伊红、Masson三色、过碘酸雪夫、谷胱甘肽-S-转移酶免疫组织化学、增殖细胞核抗原免疫组织化学染色,动态观察肝组织病理形态变化,以寻找肝细胞癌前期病变的特点。结果肝癌病理变化可分为3个阶段:肝细胞损伤阶段(2-5周):主要表现为中央静脉周围肝细胞坏死,坏死塌陷区少量细胞外基质沉积;细胞增生及肝硬化形成阶段(8-12周):肝细胞呈结节状再生,伴肝细胞异型增生,坏死塌陷区细胞外基质沉积．并逐渐形成肝硬化。肝癌形成阶段(第14周以后):此期有肝癌形成,18周成癌率为62．5％。从实验第1O周开始,嗜碱性细胞灶明显增多,部分胞质内见苍白小体,嗜碱性小细胞改变从第12周出现,增殖细胞核抗原免疫染色呈阳性,部分小细胞改变,细胞质内含脂泡,向周围肝细胞间浸润生长。结论细胞质内含苍白小体和脂肪泡,证明嗜碱性细胞灶和小细胞改变与肝细胞癌有关,其向肝细胞间的浸润生长,进一步证明其可癌变。Objective To investigate the malignant tendency of liver basophilic cells in rats by examining the liver dynamic pathological changes during the hepatocarcinogenesis induced by diethylnitrosamine （DEN）. Methods One hundred forty male Sprague-Dawley rats, about 200 g each, were randomly divided into a normal group and a model group. The model group rats were administered 1% DEN intragastrically once a week for 14 weeks. The normal control group rats were given saline instead of DEN. Seven to ten rats of the model group were sacrificed at 2, 3, 5, 8, 10, 12, 14, 18 weeks. The remaining rats were followed to the end of the experiment at 26 weeks. Histopathological changes of the livers were analyzed, and the localization of GST-P and PCNA in the livers were detected in situ by immunohistochemistry. Results According to the characteristics of the lesions in the model group, histological liver change patterns were categorized into three phases： （1） liver injury phase （2 to 5 weeks） with centrilobular necrosis, a small amount of collagen deposition in the necrotic regions with fibrous septa development and cell proliferation; （2） the cirrhosis phase （8 to 12 weeks） with significant hepatocellular regeneration and collagen deposition. As the regenerative nodules and fibrous septa formed, cirrhosis with uniform sized nodules developed in all the rats at 12 weeks. In the regenerative nodules, significant hepatocellular metamorphosis was seen; （3） In the carcinomatous transformation and nodular remodeling phase （after 14 weeks）, two types of cancer, namely hepatocellular carcinoma and cholangiocarcinoma were found. Incidence of the cancer was 62.5% at 18 weeks. Basophilic cell lesions appeared beginning at 10 weeks. Pale bodies were seen in some basophilic cells. Small cell changes appeared starting at 12 weeks. Some of these cells containing droplets like lipid vacuoles, invaded into the surrounding liver tissues. Both basophilic cell lesions and small cell changes were all positive for proli

关 键 词：癌 肝细胞 癌前期病变 细胞 嗜碱性 大鼠 二乙基亚硝胺 

分 类 号：R735.7[医药卫生—肿瘤]