二乙基亚硝胺诱导建立Apc基因突变大鼠与F344大鼠肝癌模型的比较

摘要

Objective To establish hepatocarcinoma models induced by diethylnitrosamine (DEN) in F344 rats,KAD (Kyoto Apc Delta) rats and compare the advantages and disadvantages between them.Methods Twenty-five KAD rats were randomly divided into 2 groups.The 5 rats in control group were given the normal water.The 20 rats in experimental group were given the water containing 40 μg/mL DEN for 5 weeks,and the remaining 15 weeks they were given the normal water.Every 4 weeks,part of KAD rats was sacrificed to undergo pathological examination and make pathological sections of liver tissues and tumor tissues.Twenty-five F344 rats were treated the same as KAD rats.Results Hepatocarcinoma could be induced successfully in KAD rats and F344 rats.The same pathological developing process was found in them,which was similar with human.The average of 1.00 ± 0.82 grey-white lesions could be found in 3 KAD rats (3/4) when they were induced in the 16th week,while no lesions could be found in F344 rats (0/4) at that time.Until the end of the experiments (20 weeks),3.50 ± 1.29 cancers and gray-white lesions had been developed in KAD rats,while only 1.25 ± 0.96 could be found in F344 rats.The success rate of hepatocarcinoma induction in KAD rats was better than that in F344 rats significantly (P＜0.05).Conclusion Comparing to F344 rats,KAD rats could be a better hepatocarcinoma induction model,with shorter induction time,higher sucess rate and numbers of hepatocarcinoma.KAD rat may be an ideal model for dynamically researching the hepatocarcinoma induction.%目的 采用二乙基亚硝胺(DEN)在F344大鼠、Kyoto Apc Delta(KAD)大鼠体内诱发制备肝癌模型,并比较其优劣.方法 KAD大鼠25只,随机法分组,阴性对照组(5只)给予正常饮水;DEN造模组(20只)前5周饮水中添加40 μg/mL DEN,6～20周给予正常饮水;定期解剖大鼠,肉眼观察肝脏病变并取病变组织及癌旁组织制作病理切片.25只F344大鼠采用相同方法进行实验.结果 F344大鼠和KAD大鼠均可成功诱发肝癌,且肝癌发生病理过程与人类相似.造模16周时KAD大鼠就可见灰白色病灶点,3/4大鼠成瘤,平均病灶数为1.00士0.82个;造模20周时,KAD大鼠全部(4/4)成瘤,病灶数为3.50±1.29个;而F344大鼠迟至20周时才可观察到类似病灶,3/4大鼠成瘤,病灶数为1.25±0.96个.KAD大鼠的诱导成瘤性显著高于亲代F344大鼠(P＜0.05).结论 与亲代F344大鼠相比,抑癌基因Apc突变的KAD大鼠经DEN诱导更易发生肝癌,且该模型具有肝癌诱发时间短、相同诱导时间肝癌发生率高、诱发病灶数多等优点,是化学诱发制备肝癌动物模型的良好模式动物.