p21~(HBsAg/HBsAg)转基因小鼠肝脏病理学研究

目的]观察p21HBsAg/HBsAg转基因小鼠肝脏病理学改变。方法]分别选取2,6,12,18,24月龄的SPF级p21HBsAg/HBsAg转基因小鼠和p21+/+野生型小鼠,剖检进行大体观察,取肝脏及肝脏肿瘤组织,进行组织学HE染色及电镜超微结构观察。结果]p21HBsAg/HBsAg转基因小鼠肝脏大体、光镜和电镜下均有的明显病理改变。随着月龄的增加,肝脏色暗质硬,表面有结节和肿瘤形成;光镜下,肝细胞浊肿,炎症细胞浸润,脂肪变性,点状、灶状和碎屑状坏死,非典型增生,肝细胞癌。癌细胞分化良好,类似肝细胞,形成索状和腺泡状结构。癌细胞核深染,具核分裂像。电镜下,癌细胞核变形,核膜曲折凹陷,线粒体肿胀,数目增多,脊减少。4例18月龄转基因小鼠发生肝细胞癌(4/10),6例24月龄的转基因小鼠发生肝细胞癌(6/10),其中2例发现远处转移;结论]p21HBsAg/HBsAg转基因小鼠肝脏出现明显病理损害,18月龄小鼠开始发展成高分化的肝细胞癌,高龄小鼠形成的肝细胞癌能够转移。

Study on Hepatic Pathology of p21~(HBsAg/HBsAg) Transgenic Mice

Objective] To observe the pathological changes in the livers of p21 HBsAg/HBsAg transgenic mice. Methods] The p21 HBsAg/HBsAg transgenic mice(2,6,12, 18, 24 months) in SPF grade and corresponding p21 +/+ mice were dissected and the liver and hepatic tumor tissues were extirpated for the examination by histological HE staining and electron microscopy. Results] Distinct pathological changes appeared in the liver of p21 HBsAg/HBsAg transgenic mice both macroscopically and microscopically. With the increase on age, the liver of the transgenic mice turned to be dark and sclerotic with scattered formation of nodules and tumors. Under light microscope, the liver cells were swollen and inflammatory cell infiltration occurred. Fatty degeneration appeared with punctuate, focal and crumblike necrosis. Atypical hyperplasia and hepatocellular carcinoma (HCC) developed. Resembling normal hepatocytes, hepatpocarcinoma cells were well differentiated, forming cord-like and acinar-like structures. The nuclei of carcinoma cells are dark stained with karyokinetic figures and aberrated with invagination of nuclear membrane under electron microscope. Mitochondria distended, manifolded and the ridges reduced. HCC were found in four cases of 18 months old p21 HBsAg/HBsAg transgenic mice (4/10, 40%), and six cases of 24 months (6/10,60% ) respectively, of which metastasis occurred in two cases. Conclusions] Obviously pathogenic changes occurred in the liver of p21 HBsAg/HBsAg transgenic mice. Well differentiated hepatocarcinoma became to arise in the mice at the age of 18 months. Metastasis of HCCs would happen in elderly transgenic mice.