抗结核药物致肝损伤动物模型的探讨

Discussion on animal model of liver injury caused by anti-tuberculosis drugs

目的:探讨乙胺吡嗪利福异烟片(Ⅱ)在不同剂量下致大鼠肝损伤的程度,从而选出合适的造模方案。方法:选取SD大鼠40只,雌雄各半,适应性喂养一周后随机分成四组,依次是空白对照组、0.378 g/(kg·d)剂量组、0.756 g/(kg·d)剂量组和1.89 g/(kg·d)剂量组。按大鼠的生活习性每天按时灌胃一次。分别在开始给药前及给药21 d后进行内眦静脉取血,测定各组大鼠肝功指标,并用SPSS 19.0进行分析。同时留取大鼠肝脏组织制作病理切片观察。结果:可见四组大鼠的ALT、AST和TBiL的含量比较均有差异(P<0.05);两两比较发现,1.89 g/(kg·d)剂量组肝功指标ALT、AST和TBiL的含量均高于空白对照组、0.378 g/(kg·d)剂量组和0.756 g/(kg·d)剂量组(P<0.05),0.378 g/(kg·d)剂量组和0.756 g/(kg·d)剂量组分别与空白对照组的TBiL的含量有差异(P<0.05);0.756 g/(kg·d)剂量组AST的含量与0.378 g/(kg·d)剂量组比较有差异(P<0.05)。各组大鼠的肝脏病理切片对比可见:1.89 g/(kg·d)剂量组的病变程度最为严重:发生明显脂肪变性,门管区可见炎细胞浸润,点状坏死;而0.378g/(kg·d)剂量组和0.756g/(kg·d)剂量组病理改变则不明显。结论:抗结核药致肝损伤大鼠模型造模成功的最佳剂量是1.89 g/(kg·d)的乙胺吡嗪利福异烟片(Ⅱ)给药21 d。

Objective:To investigate the degree of liver injury induced by ethylamine pyrazine rifampicin tablets(Ⅱ)in rats,so as to select a suitable scheme for modeling.Methods:40 SD rats,half male and half female,were randomly divided into four groups after adaptive feeding for one week.The rats were randomly divided into four groups:blank control group,0.378 g/kg/d drug group,0.756 g/kg/d drug group and 1.89 g/kg/d drug group.According to the living habits of rats,the rats were given intragastric administration on time once a day.Blood samples were taken from medial canthus vein before administration and 21 days after administration,and liver function indexes of rats in each group were measured and analyzed by SPSS19.0.At the same time,the liver tissues of rats were taken to make pathological sections.Results:There were differences in the contents of ALT,AST and TBiL among the four groups(P<0.05).The results of pairwise comparison showed that the contents of ALT,AST and TBiL in 1.89 g/kg/d dose group were higher than those in blank control group and 0.378 g/kg/d and 0.756 g/kg/d dose groups(P<0.05).There was a difference in the content of TBiL between the 0.378 g/kg/d and 0.756 g/kg/d dose group(P<0.05).The content of AST in the 0.756 g/kg/d dose group was different from that in the 0.378 g/kg/d dose group(P<0.05).The comparison of liver pathological sections of rats in each group showed that the pathological changes in the 1.89 g/kg/d drug group were the most serious:obvious steatosis,inflammatory cell infiltration and punctate necrosis in the portal area,while the pathological changes in the 0.378 g/kg/d and 0.756 g/kg/d dose groups were not obvious.Conclusion:The optimal dose of ethylamine pyrazine rifampicin isoniazine tablets(Ⅱ)for 21 days is 1.89 g/kg/d for the rat model of liver injury induced by antituberculosis drugs.