CCl_4,D-Gal,ANIT致小鼠肝损伤模型的实验研究

Study on liver injury models induced by CCl4 DGal and ANIT in mice

目的观察３种化学性肝毒剂不同时间对小鼠肝损伤的影响．方法①ＣＣｌ４试验：取小鼠６０只，随机分６组，每组１０只．每组代表一个观察时间点，即２４，４８，７２，９６，１２０，１４４ｈ．并设相应生理盐水（ＮＳ）对照组．６０只小鼠分别一次攻毒，１５ｇ／ＬＣＣｌ４１０ｍｇ／ｋｇ，ｉｇ，待小鼠中毒后，按上述不同时间点，分别摘取小鼠眼球取血，分离血清，经生化自动测定仪分别测定血清ＡＬＴ，ＡＳＴ和ＢｉｌｉＴ的含量，并切取小鼠肝脏标本作病理切片观察．②ＤＧａｌ试验：动物分组、实验方法和观察指标同ＣＣｌ４．中毒量为８００ｍｇ／ｋｇ，ｉｐ．③ＡＮＩＴ试验：动物分组、实验方法和观察指标同ＣＣｌ４．中毒量为１００ｍｇ／ｋｇ，ｉｇ．结果ＣＣｌ４（１０ｍｇ／ｋｇ，ｉｇ）和ＤＧａｌ（８００ｍｇ／ｋｇ，ｉｐ）均于小鼠中毒后２４ｈ～４８ｈ肝损伤明显，血清ＡＬＴ，ＡＳＴ显著升高；ＡＮＩＴ（１００ｍｇ／ｋｇ，ｉｇ）致小鼠肝损伤于４８ｈ～７２ｈ最重，肝细胞、肝内胆管病变和血清ＡＬＴ，ＡＳＴ，ＢｉｌｉＴ升高明显．随着小鼠中毒时间的延长，ＣＣｌ４和ＤＧａｌ中毒分别于１４４ｈ和９６ｈ肝损伤基本恢复正常，而ＡＮＩＴ损伤小鼠肝脏病变持续１４４ｈ仍未恢复?

IM To study the dynamic alterations of liver function and pathology of three liver injury models induced by CCl4, DGal and ANIT in mice.METHODS The models were induced by 15g/L CCl4 10mg/kg, ig, DGal 800mg/kg, ip, and ANIT 100mg/kg, ig, respectively. Kunming mice were randomly divided into 6 groups (10 for each) for each model. The serum samples were taken by excising out eyeball at 24,48,72,96,120 and 144h, respectively after poisoning. The ALT, AST and BiliT were determined using automatic biochemical analyzer. Livers were cut out for pathological examination.RESULTS The concentration of serum ALT and AST increased significantly (P<001) 24h-48h after poisoning by CCl4 and DGal. But livers were injured most significantly by ANIT between 48h and 72h, and there were marked pathological changes of liver cells and hepatic bile ducts with significant increase of serum BiliT level. The livers injured by CCl4 and DGal became normal in 144h and 96h, respectively, while pathological changes of the livers injured by ANIT remained unchanged in 144h.CONCLUSION CCl4 or DGal induced liver injury models in mice are useful in the study of effects of drugs on ALT, while ANIT induced model is suitable in studying the drugs on both bilirubin and enzyme (ALT and AST). The appropriate time to collect samples is within 24h to 48h in CCl4 or DGal models and 48h to 72h in the ANIT model after poisoning..