BALB/c小鼠肝癌模型建立及其形态学特征分析

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目的:建立BALB/c小鼠肝癌动物模型,并研究其超微结构的特点,为开展肝细胞癌相关实验研究奠定基础。方法:66只正常雄性成年BALB/c小鼠完全随机分为5组,即实验A、B、C、D组和对照组,实验组每组14只,对照组10只。采用二乙基亚硝胺(DEN)/四氯化碳(CCl4)/乙醇的联合诱导方式喂养实验组小鼠;于给药后第60、90、120和150天,分别取实验A、B、C和D组小鼠肝脏组织;于给药后第150天取对照组小鼠肝脏组织。观察小鼠肝脏病变的发生情况及其超微结构的改变,并利用RT-PCR检测病变肝脏组织不同时期小鼠甲胎蛋白(mAFP)的变化情况。结果:对小鼠肝脏组织行病理学检查发现,对照组肝脏未见异常,给药后第60天实验A组小鼠肝脏炎症发生率为64.28%(9/12),第90天实验B组小鼠肝脏轻度纤维化发生率为64.28%(9/12),第120天实验C组小鼠肝硬化发生率为71.43%(10/12),第150天实验D组小鼠肝脏肿瘤性病变发生率为64.28%(9/12);以上时间点各实验组小鼠肝脏病变发生率均明显高于对照组,P<0.05。mAFP阳性表达在给药60d后出现;第150天时透射电镜下观察到的形态特征符合肝癌。结论:利用化学致癌剂和肿瘤促进剂,成功建立了甲胎蛋白分泌型BALB/c小鼠肝癌动物模型,该方法诱导时间相对较短,病变过程和超微结构的改变均与人类肝癌发病特点类同,是研究肝癌发生发展的理想实验动物模型。 OBJECTIVE: To establish an animal model of hepatocellular carcinoma in BALB / c mice and to study the ultrastructural characteristics of the hepatocellular carcinoma in BALB / c mice so as to lay the foundation for further studies on hepatocellular carcinoma. Methods: Sixty-six adult male adult BALB / c mice were randomly divided into five groups: experimental groups A, B, C, D and control group, with 14 in each group and 10 in control group. The mice in the experimental group were fed with diethylamine (DEN) / carbon tetrachloride (CCl4) / ethanol. At the 60th, 90th, 120th and 150th days after the administration, the experimental groups A, B , C and D mice liver tissue; 150 days after administration of control mice liver tissue. The occurrence of liver lesions and ultrastructural changes in mice were observed. The changes of the expression of mAFP in different stages of liver tissues were detected by RT-PCR. Results: The pathological examination of liver tissue of mice showed no abnormalities in the liver of the control group. The incidence of hepatic inflammation in the experimental group A was 64.28% (9/12) on the 60th day after the administration. On the 90th day, the experimental group B The incidence of mild liver fibrosis was 64.28% (9/12) in mice. The incidence of cirrhosis was 71.43% (10/12) in group C on the 120th day. The liver tumor of group D on the 150th day The incidence of pathological changes was 64.28% (9/12). The incidences of liver lesions in the experimental groups were significantly higher than those in the control group at the above time points (P <0.05). The positive expression of mAFP appeared after 60 days of administration; the morphological features observed by transmission electron microscopy on the 150th day were in accordance with the liver cancer. Conclusion: The animal model of AFP-secreting BALB / c mice hepatocarcinoma was successfully established by using chemical carcinogens and tumor promoters. The induction time was relatively short, and the pathological process and ultrastructure changes were both associated with the incidence of human hepatocellular carcinoma Similar, is to study the occurrence and development of liver cancer ideal experimental animal model.
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