四氯化碳诱导的小鼠肝损伤模型比较

目的：比较四氯化碳（carbon tetrachloride,CCl4）诱导小鼠急性、亚急性、慢性肝损伤模型的差异,探讨稳定、可靠的小鼠肝损伤模型复制方法。方法：以CCl4油溶液（油为食用植物油）为材料,分别通过腹腔注射、皮下注射、灌胃等给药方式,固定给药时间,观察血清谷草转氨酶（AST）、谷丙转氨酶（ALT）活性及肝组织细胞形态的变化,考察肝损伤模型复制的的稳定性、可靠性。结果：腹腔注射不同浓度的CCl4均可产生急性肝损伤,使血清ALT明显升高,但只有高剂量才能升高AST;皮下注射不同浓度的CCl4均可产生亚急性肝损伤,CCl4中剂量组不仅可使血清ALT明显升高,还能升高AST;灌胃不同浓度的CCl4均可产生慢性肝损伤,CCl4各剂量组不仅可使血清ALT明显升高,还能升高AST,作用稳定,且呈浓度依赖性。肝组织病理切片显示急性、亚急性肝损伤模型肝组织坏死严重,组间没有明显区别;而慢性肝损伤模型出现肝细胞变性、部位肝组织坏死,浓度间呈现不同趋势。结论：CCl4诱导的慢性肝损伤模型复制稳定、病理特征明显,更有利于用于考察药物的作用及机制。

Model Comparison in Liver Injury in Mice Induced by CCl_4

Objective：To compare the difference among acute、subacute、chronic liver injury of mice induced by CCl4,exploring a stable、reliable method to create a liver injury model in mice.Methods：The model of liver injury was made by CCl4 oil solution with subcutaneous injection、intraperitoneal injection or by gavage,and fixed the delivery time.Observation of the changes of plasma ALT、AST and liver slices,to investigate stability and reliability of the method.Results：All of different concentrations of CCl4 can produce acute,subacute,chronic liver injury,and in aspects of acute liver injury,ALT increased significantly,the level of AST elevated only in high dose groups.As for subacute liver injury,middle dose can increase both ALT and AST obviously.Concerning the chronic liver injury,plasma ALT and AST in all dose groups were markedly higher than those in the control group in a concentration- dependent manner.Conclusion：The model of chronic liver injury induced by CCl4,was the most stable,and clinicopathological features were obvious,so it was beneficial to investigate the roles and mechanism of drugs.