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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 observe the occurrence and development of hepatocellular carcinoma (HCC) dynamically and investigate the morphological characteristics and carcinogenesis of HCC precancerous lesions. Methods A total of 145 male Sprague-Dawley rats were randomly divided into model group and normal control group. The rats in model group were intragastrically administrated with 1% diethylnitrosamine 60 mg / kg once a week for the first 12 weeks To 40mg / kg to 14 weeks after withdrawal; normal control with isotonic saline gavage. Rats were sacrificed in batches on the 2nd, 3rd, 5th, 8th, 10th, 12th, 14th and 18th week after the start of the experiment. The remaining rats were sacrificed at the 26th week. Liver tissue hematoxylin-eosin, Masson trichrome, periodic acid Schiff, glutathione-S-transferase immunohistochemistry, proliferating cell nuclear antigen immunohistochemical staining, dynamic observation of liver pathological changes in order to find the liver Features of precancerous lesions. Results The pathological changes of liver cancer can be divided into three stages: the stage of liver cell injury (2-5 weeks): the main manifestations of liver cell necrosis around the central vein, a small amount of extracellular matrix deposition in necrotic areas; cell proliferation and cirrhosis of the formation phase (8 -12 weeks): nodular liver cell regeneration, with hepatocyte dysplasia, necrosis of the extracellular matrix deposition area. And gradually formed cirrhosis. Liver cancer formation stage (after 14 weeks): This period of liver cancer formation, 18 weeks cancer rate was 62.5%. From the first 10 weeks of experiment, basophilic foci increased significantly, some of the cytoplasm see pale bodies, basophils changed from the 12th week, proliferating cell nuclear antigen immunostaining was positive, some small cells changed, the cytoplasm Contains liposomes, infiltration of growth around the hepatocytes. Conclusions The cytoplasm contains pale bodies and fat vesicles, demonstrating that basophilic cell foci and small cell changes are associated with hepatocellular carcinoma, which are infiltrating into hepatocytes and further demonstrating their carcinogenesis.