烷基三甲铵钙土霉素对小鼠的亚急性毒性试验

Subacute toxicity testing of oxytetracycline calcium quaternary in mice

为了评价烷基三甲铵钙土霉素的安全性，为今后系统地研究其药理作用以及为临床安全用药提供试验依据。在小鼠急性毒性试验的基础上，选用80只昆明系小鼠随机分为烷基三甲铵钙土霉素低、中、高剂量组和空白对照组，药物组连续30d分别灌服18．83mg／kg、75．32mg／kg、302．7mg／kg药物，通过临床观察、血液学分析、血液生化检测、脏器系数和病理学检查，系统地评估烷基三甲铵钙土霉素对小鼠的亚急性毒性作用。结果表明，各剂量组小鼠精神状况良好，无死亡。试验过程中低、中剂量组小鼠的体重、脏器系数、血液学指标、血液生化指标、组织病理学变化等各项指标与对照组比较均无显著性差别（P〉0．05）；而高剂量组小鼠增重指数差异显著（P〈0．05），长期给药后高剂量组小鼠的脾、肺、肾的脏器系数有显著改变（P〈0．05），高剂量组小鼠血液中谷草转氨酶、尿素氮、肌酐及碱性磷酸酶水平显著性升高（P〈0．05），谷草转氨酶／谷丙转氨酶活性比值显著性降低（P〈0．05）；高剂量组肝、肾部分细胞发生轻微肿胀，肺间质轻微增宽。提示长期大剂量使用烷基三甲铵钙土霉素可能造成小鼠轻微的肝、肾组织损伤。本试验结果提示，烷基三甲铵钙土霉素的毒性很低，临床用药较为安全。

To evaluate the safety of oxytetracycline calcium quaternary（OTC-Ca-DTMAC） and to study its pharmacological effect in future,subacute toxicity tests on kunming mice were evaluated. 80 Kunming mice were randomly divided into 4 groups with 20 mice（half male and half female） in each group,and those mice were respectively treated with 18.83 mg/kg,75.32 mg/kg,302.7 mg/kg for 30 days,or ultrapure water solvent as control,and then subacute toxic effects of OTC-Ca-DTMAC on mice were evaluated by clinical observation,blood biochemical tests,organ coefficient and pathological changes, ln result,there were no significant differences between the low and medium dose group in the experiment（P〉0.05）,but high dose group had significant differences（P〈0.05） with the control group. After long-term administration,the organ coefficients of the spleen,lung and kidney in the high dose group were significantly changed（P〈0.05）with the control group,and liver,kidney cells were slightly swollen,and pulmonary interstitial was slightly widened among the high dose group. The overrall results showed that oxytetracycline calcium quaternary had no subacute toxic effects in mice.