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中国应用生理学杂志 ›› 2021, Vol. 37 ›› Issue (5): 475-479.doi: 10.12047/j.cjap.6110.2021.063

• 研究论文 • 上一篇    下一篇

酮康唑对小鼠肝脏和睾丸生理功能的影响*

贺英昊, 方情, 杨玲玲, 陈思敏, 骆燕萍, 钱虹, 齐敏友   

  1. 浙江工业大学药学院药理研究所, 杭州 310014
  • 收稿日期:2020-06-09 修回日期:2021-01-27 出版日期:2021-09-28 发布日期:2021-11-24
  • 通讯作者: Tel: 0571-88320535; E-mail: qiminyou@163.com
  • 基金资助:
    *浙江省自然科学基金(LY16H280013); 浙江工业大学大学生创新创业训练计划(2018101,2018103)

Effects of ketoconazole on physiological function of liver and testis in mice

HE Ying-hao, FANG Qing, YANG Ling-ling, CHEN Si-min, LUO Yan-ping, QIAN Hong, QI Min-you   

  1. Institution of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China
  • Received:2020-06-09 Revised:2021-01-27 Online:2021-09-28 Published:2021-11-24

摘要: 目的: 观察不同剂量的酮康唑(KCZ)对昆明小鼠的肝脏和睾丸生理功能的影响。方法: 将 40 只雄性昆明小鼠随机分为 4 组(n=10):正常组、酮康唑低剂量组(30 mg/kg)、酮康唑中剂量组(50 mg/kg)、酮康唑高剂量组(70 mg/kg)。药物组小鼠按0.1 ml/10 g给药体积每日单次皮下注射酮康唑,酮康唑低、中、高剂量组药物浓度各为3 mg/ml、5 mg/ml、7 mg/ml,正常组注射等量生理盐水,连续 3 周。测定血清谷草转氨酶(AST)、谷丙转氨酶(ALT),以及睾丸组织 γ-谷氨酰胺转肽酶(γ-GT)、乳酸脱氢酶(LDH)和酸性磷酸酶(ACP)活性;HE 染色观察肝脏、睾丸病理组织改变。结果: 与正常组比较,酮康唑组AST、ALT活性显著升高(P<0.01);γ-GT、ACP、LDH活性显著下降(P<0.01),且以上指标的改变均随剂量增加而损伤加重。HE 染色显示小鼠肝细胞变性,排列松散,胞质色浅;睾丸曲细精管管腔增大,各级生精细胞、精子数量减少。结论: 酮康唑能导致小鼠肝脏、睾丸组织生理功能损伤与病理组织学改变,升高肝转氨酶水平,降低睾丸特异性酶活性,且损伤程度随剂量的升高而增大。

关键词: 酮康唑, 肝功能, 睾丸, 小鼠

Abstract: Objective: To investigate the effects of different doses of ketoconazole (KCZ) on the physiological functions of the liver and testis in Kunming mice. Methods: Forty male Kunming mice were randomly divided into four groups (n=10): normal group, KCZ low-dose group (30 mg/kg), medium-dose group (50 mg/kg), and high-dose group (70 mg/kg). The mice in the drug groups were injected subcutaneously (0.1 ml/10 g) with the corresponding dose of KCZ once a day, and the concentrations of KCZ in the KCZ low, middle, and high dose groups were 3 mg/ml, 5 mg/ml and 7 mg/ml respectively, and the normal group was injected with the same amount of normal saline for 3 weeks. The activities of aspartate transaminase (AST) and alanine aminotransferase (ALT) in serum, and γ-glutamyl transpeptidase (γ-GT), lactate dehydrogenase (LDH) and acid phosphatase (ACP) in testicular tissue were measured. HE staining was used to observe the pathological changes of the liver and testis. Results: Compared with the normal group, the activities of AST and ALT were increased significantly (P<0.01), and the activities of γ-GT, ACP and LDH were decreased markedly in KCZ groups (P<0.01). KCZ could affect the above indexes in a dose-dependent manner. HE staining showed that the hepatocytes were denatured, arranged loosely, and the cytoplasm was light in color. The lumen of the seminiferous tubules of the testis were enlarged, and the number of spermatogenic cells and sperm at all levels were decreased. Conclusion: KCZ could cause physiological function damage and pathological histological changes of the liver and testis, increase the levels of liver transaminase, reduce the activities of testicular specific enzymes of mice. Besides, the degree of damage was increased with the increase of dose.

Key words: Ketoconazole, liver function, testicle, mice

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