酮康唑对可卡因致小鼠肝毒性的保护作用  

Protective effects of ketoconazole against cocaine-induced hepatotoxicity in mice

作　　者：丁兆丰[1] 贾凤兰[1] 阮明[1] 张宝旭[1] 

机构地区：[1]北京大学公共卫生学院毒理学系,北京100083

出　　处：《中国药理学与毒理学杂志》2006年第5期399-404,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30171122)~~

摘　　要：目的澄清酮康唑对可卡因所致小鼠肝脏损伤具有有害的还是有益的影响。方法采用可卡因致小鼠肝损伤模型,分别使用预防性和治疗性给药两种实验方法。所有动物处死后,观察血清中谷丙转氨酶(GPT)、谷草转氨酶(GOT)、乳酸脱氢酶(LDH)的活性,测定肝脏中的还原性谷胱甘肽(GSH)和氧化性谷胱甘肽(GSSG)的含量变化和丙二醛(MDA)的含量,并进行组织病理学检测。结果单纯给予可卡因,血清中GPT,GOT和LDH活性升高,肝组织中MDA含量增加,GSH/GSSG比值下降。与单纯给予可卡因相比,预防性或治疗性给予酮康唑能够显著地降低血清中GPT,GOT和LDH活性,并且肝组织中MDA含量下降,GSH/GSSG比值回升。经过酮康唑处理后,肝脏的病理损伤程度也有明显的改善。结论酮康唑能对可卡因引起的急性肝脏损害有一定的保护作用。AIM To clarify whether ketoconazole has protective effects against or harmful influences on cocaine-induced hepatotoxicity in mice. METHODS Animal experimental models of hepatotoxicity induced by cocaine were applied to investigate the preventive and theropeutical effects, respectively. Serum alanine aminotransferase （GPT）, aspartate aminotransferase （GOT）, and lactate dehydrogenase （LDH） levels were determined. Contents of liver reduced glutathione （GSH） and oxidized glutathione （GSSG） as well as malondialdehyde （MDA） were examined. And histopathological examine was also made. RESULTS Mter the administration of cocaine, the levels of serum GPT, GOT and LDH were increased. The ratio of GSH/GSSG was decreased and the content of MDA was increased. With the pretreatment or posttreatment of ketoconazole compared to the treatment of cocaine only, the serum enzyme levels were decreased and the ratio of GSH/GSSG and the content of MDA were close to the normal. Significant amelioration in liver histopathology was also presented in the group treated with ketoconazole. CONCLUSIONS This observation suggested that ketoconazole have preferably protective effect against cocaine-induced hepatotoxicity in mice.

关 键 词：肝 毒性 可卡因 酮康唑 

分 类 号：R96[医药卫生—药理学]