小鼠长期服用阿苯达唑对肝脏的影响

Effect of Long-term Use of Albendazole on Mice Liver

目的观察服用阿苯达唑1～16周对小鼠血清中7项肝功能指标和肝组织超微结构的影响。方法180只昆明雌性小鼠随机均分为给药组和阴性对照组。给药组小鼠灌服阿苯达唑136.3 mg/(kg.d),对照组给予等量生理盐水。给药1、2、4、6、8、10、12、14和16周时,两组各时段随机取10鼠,眼内眦静脉取血,分离血清,检测肝功能指标,即丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、直接胆红素(DBL)、间接胆红素(IBIL)、白蛋白(ALB)和球蛋白(GLB)等7项指标;10鼠中5鼠取肝组织,固定染色后透射电镜观察,进行病理评分,将两组比较后有统计学意义的肝功能指标作为自变量,病理评分作为因变量进行单因素线性回归分析。结果在给药各时间段,给药组的DBL、IBIL、ALB和GLB水平,与阴性对照组比较,差异无统计学意义(P>0.05)。给药12周组ALT(55.2±23.7)、AST(176.4±49.2)和ALP(141.1±19.4)等3项指标值均高于其余给药组,且明显高于阴性对照组(35.5±8.6、108.2±21.9和84.0±24.8)(均P<0.05)。给药2、8、10、12和14周组,肝组织病理评分为11.8±4.8、10.6±4.8、13.6±3.5、29.8±10.7和5.6±2.5,明显高于阴性对照组(0.8±0.4、1.2±0.8、2.4±2.0、1.2±0.4和1.4±1.1)(均P<0.05)。以ALT、AST和ALP为自变量、病理评分为因变量的3组单因素线性回归方程中,AST所属方程线性回归拟合度最佳,回归方程为Y=-17.616+0.188X。结论小鼠长期服用棘球蚴病治疗剂量的阿苯达唑可致ALT、AST、ALP等3项肝酶指标明显升高,并引起轻度的肝组织病理改变。

Objective To observe the change in serum levels of alanine aminotransferase （ALT）, aspartate transaminase （AST）, alkaline phosphatase （ALP）, direct hilirubin （DBL）, indirect bilirubin （IBIL）, albumin （ALB） and globulin （GLB）, and mouse liver uhrastructure during 1-16 weeks of albendazole treatment. Methods 180 female Kunming mice were divided randomly into alhendazole treatment group and negative control group. Each mouse of albendazole treatment group was treated with 136.3 mg/（kg.d） alhendazole. The mice in control group were given same amount of physiological saline. After 1, 2, 4, 6, 8, 10, 12, 14 and 16 weeks of treatment, 10 mice from each group were randomly selected, serum samples were collected and analyzed for the above seven liver function indices. Pathological changes of liver were observed by transmission electron microscopy. Linear regression analysis was conducted for the relationship between liver function indices（dependent variable） and pathological scores （independent variable）. Results During 1-16 weeks of albendazole treatment, there was no significant difference in serum levels of DBL, IBIL, ALB and GLB between albendazole treatment group and control group. Compared with other treatment period, after 12 weeks of treatment the serum levels of ALT（55.2±23.7）, AST（176.4±49.2） and ALP（141.1±19.4） in albendazole treatment group were higher than that of the control （35.5±8.6, 108.2±21.9, 84.0±4.8） （P〈0.05）. After 2, 8, 10, 12 and 14 weeks of treatment, the pathological score of alhendazole treatment group was 11.8±4.8, 10.6±4.8, 13.6±3.5, 29.8±10.7, and 5.6±2.5, respectively, which was higher than that of the control （0.8±0.4, 1.2±0.8, 2.4±2.0, 1.2±0.4, 1.4±1.1） （P〈0.05）. Among the three liver function indices AST, ALT and ALP, AST was the best fit index for linear regression. Theregression formula was Y=-17.616±0.188X. Conclusion Long-term treatment with albendazole at a dosage of 136.3 mg/（kg .d） for mice can cause significant elevation of serum levels of ALT, AST and ALP, and result in mild pathological changes in the liver.