摘要
为了更深入地研究酮康唑对肝的毒性损害,采用杂种犬作了为期一个月的长期毒性实验,分别用电镜和光镜技术对犬的肝进行了细胞超微结构和病理组织学观察。实验设3个剂量组,给药剂量为大剂量组70mg/(kg·d),中剂量组35mg(kg·d),小剂量组为17.5mg/(kg·d),(分别相当于临床剂量的21、10.5和5.2倍),另一组为溶媒对照组,连续灌胃30天。电镜结果表明:中剂量组肝细胞线粒体肿胀变性,大剂量组肝细胞质中出现大量髓样小体,其中大剂量组中有两只动物在给药15天内先后中毒死亡。血液生化检查结果提示,大、中剂量组血清谷丙转氨酶、血清碱性磷酸酶、血清乳酸脱氢酶活性增高,血清总胆红素含量明显增高,小剂量组各项指标无异常。实验结果表明,酮康唑在一定剂量下可导致药物中毒性肝损伤。
In order to study the toxic damage of Ketoconazole on liver, we made a one-month toxicity test in dogs and observed the liver's ultrastructure and pathological histology by electron microscopy (EM) and light microscopy. Experimental animals were divided into three dosage groups. Dosages of 70, 35 and 17. 5mg/(kg ·d) (equivalent to 21, 10. 5 and 5. 2 times the clinical dosage) were given to dogs. Another group was solution control group. EM results showed the swelling and degeneration of the mitochondria of liver cells in the median dosage group. There were a number of myelinoid bodies in the cytoplasm of liver cells in the large dosage group. Two dogs died from toxicosis within 15 days. Blood examination revealed that the activities of ALT, ALP and LDH, and the contents of T-BILL in serum increased in the large and median dosage group. There were no significant changes in the small dosage group. The results indicate that Ketoconazole can cause drug toxic hepatic damage at a certain dosage.
出处
《解剖学杂志》
CAS
CSCD
北大核心
1996年第1期71-74,共4页
Chinese Journal of Anatomy
