对活体状态下大鼠肝癌模型早期诊断的研究

The research of early diagnosis for the rat hepatom model

目的:探讨活体状态下对大鼠肝癌模型实现早期诊断的方法。方法:将40只幼龄雄性大鼠随机分为正常组、间断性小剂量二乙基亚硝胺(Diethylnitrosamine,DENA)诱癌组(n=20只)。正常组自由饮用生理盐水,间断性给药组对大鼠给予0.2%DENA灌胃,按10mg/kg给药,每周5次。两实验组第15周停药。第20周所有大鼠磁共振(Magnetic resonance,MRI)检查,称重,采集血液标本作甲胎蛋白(α-foetoprotein,AFP)和肝功能检测,所得数据导入非条件Logistic回归模型分析,取组织标本做HE染色病理标本。结果:实验组诱癌率为85%,MRI对肝癌诊断准确率为94.1%。Logistic回归分析显示血浆谷丙转氨酶(Alanine transarninase,ALT)与大鼠是否成癌关系最为密切。结论:间断性给药法结合大鼠血浆ALT值的持续监测,对ALT异常的大鼠进行MRI检查,有利于在经费和时间有限的情况下,早期诊断肝癌,避免建模中过高的死亡率和肝外转移率,为后续研究打下基础。

Objective：to research how to implement early diagnosis for the hepatom model when the rats are alive.Methods：40 young male Wistar rats（30～40 d）were randomly divided into two groups,20 rats in each group（the control group and the interruptedly low doses experimental group）.The control group was fed with physiologic saline for 20 weeks.The interruptedly low doses experimental group was fed with 0.2%diethylnitrosamine（DENA）at a dose of 10 mg/kg every week 5 times.The experimental group was induced for 15 continuous weeks.All of them were sacrificed at the 20th week when the rats were inspected by MRI and weighed.The histological changes of liver tissue were observed under microscope.The levels of liver function andα-foetoprotein（AFP）were recorded。all the factors were put into a logistic regression model for multivariate analysis.Results：the induction achievement ratio of hepatoma model in Wistar rats was 85%.The correct rate of MRI for hepatoma was 94.1%.With multivariate analysis,only 1 of the 7 variables in the final logistic regression model was statistically significant：alanine aminotransferase（ALT）.Conclusion：Through giving rats low doses of DENA interruptedly and performing MRI for inspecting pathological changes of rat livers with anomaly increased levels of plasma ALT,we can implement early diagnosis for the hepatom model to decrease the rate of death and extrahepatic metastasis when fund and time is limited.