年龄与性别对异硫氰酸萘酯中毒小鼠急性肝损伤的影响

目的：研究年龄与性别对异硫氰酸萘酯（ANIT）中毒所致小鼠急性肝损伤的影响。方法：采用一次性ANIT 75mg/Kg经口灌胃染毒致5、10、20周龄雌雄性小鼠急性肝损伤,通过肝功能（ALT,AST、DBil）检测和肝组织HE染色病理学检查,观察不同性别和年龄小鼠急性肝损伤变化特征。结果：ANIT 75mg/Kg经口灌胃染毒可致5周龄小鼠血清ALT、AST和DBil明显上升,肝组织学呈明显淤胆改变。随着年龄增加,ANIT中毒所致小鼠上述改变更加明显。雄性小鼠明显重于雌性小鼠,雌性小鼠怀孕后肝损伤胆红素上升,ANIT 100mg/Kg经口灌胃可致雄性老年小鼠出现死亡。结论：ANIT中毒所致小鼠急性肝损伤与年龄和性别密切相关,毒性以雄性老年小鼠更加明显,只适合用于制作原发性硬化性胆管炎（PSC）动物模型。

Effects of age and gender on α-naphthylisothiocyanate-induced acute toxic liver injury in mice

Objective： To study the effects of age and gender on α-naphthylisothiocyanate（ ANIT）-induced acute toxic liver injury in mice. Methods： Male and female mice of 5,10,20 weeks olds were gavaged orally with ANIT 75 mg /Kg once a time to induce acute liver injury,serum biochemical parameters of liver function including alanine aminotransferase（ ALT） and aspartate aminotransferase（ AST）,direct bilirubin（ DBil） ] and HE staining of liver tissue were detected to observe the characteristic changes of acute liver injury with different age and gender. Results： Oral gavage of ANIT 75 mg /Kg caused significant increase of serum ALT,AST and DBil in mice of 5 weeks old,apparent bile stasis change of liver tissue. With the increase of age,the above changes became more evident. The above changes were more severe in male mice than in female mice,meanwhile after pregnancy in female mice liver injury became more severe, and more, ANIT 100 mg /Kg led to deaths in male aged mice. Conclusion： The acute liver injury in mice induced by ANIT is closely related with age and gender,the injury is more pronounced in male aged mice,which is only suitable to produce animal model of primary sclerosing cholangitis.