1,3-二苯-1,3-丙二酮对可卡因致小鼠肝毒性及神经毒性的保护作用  

PROTECTIVE EFFECT OF 1,3-DIPHENYL-1,3-PROPANEDIONE ON LIVER TOXICITY AND NEUROTOXICITY INDUCED BY COCAINE IN MICE

作　　者：吕艳[1] 丁兆丰[1] 马秋霞[1] 何月莹[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系,北京100191

出　　处：《中国药物依赖性杂志》2011年第2期87-92,100,共7页Chinese Journal of Drug Dependence

基　　金：国家科技重大专项"重大新药创制"资助项目(编号2009ZX09103-007)

摘　　要：目的:探讨1,3-二苯-1,3-丙二酮(DPPD)对可卡因致小鼠急性肝损伤及神经毒性的保护作用。方法:可卡因急性肝损伤模型采用♂C57BL/6N小鼠,DPPD(200,400,800 mg·kg–1/d,ig)预给药4 d,末次给药30 min后,sc可卡因70 mg·kg-1造模,24 h后处死,测定血清ALT,AST,LDH的活性及肝脏MDA含量,观察肝脏病理变化。DPPD抗可卡因神经毒性实验采用♂ICR小鼠,DPPD预给药3 d(给药剂量同前),末次给药30 min后,sc可卡因20mg·kg-1造模,记录小鼠0-180 min的活动次数。结果:可卡因70 mg·kg-1致部分小鼠死亡(5/7),存活小鼠血清ALT,AST,LDH活性及肝脏MDA含量显著升高,肝脏病理损伤明显,而DPPD预给药组无死亡,血清ALT,AST,LDH活性及肝脏MDA含量显著降低,肝脏损伤明显改善,呈剂量-效应关系;DPPD抗可卡因神经毒性研究发现,DPPD预给药组小鼠自主活动量较模型组显著降低。结论:DPPD对可卡因致小鼠急性肝毒性及神经毒性有拮抗作用。Objective： To evaluate the protective effect of 1,3-diphenyl-1,3-propanedione（DPPD）on acute liver injury and neurotoxicity induced by cocaine in mice.Methods：Male C57BL/6N mice were pretreated with DPPD（200,400,800 mg·kg-1/d,ig）for 4 days prior to cocaine（70 mg·kg-1,sc）exposure,which was implemented 30 minutes later after DPPD administration on day 4 to make acute liver injury model.24 hours later,serum ALT,AST and LDH activities and malondialdehyde（MDA）in liver homogenate were assayed and liver tissues were collected for histopathological assessment.Male ICR mice were pretreated with DPPD（200,400,800 mg·kg-1/d,ig,3 days）prior to cocaine（20 mg·kg-1,sc）exposure,which was implemented 30 minutes later after DPPD administration on day 3.And the locomotor activity in 0-180 minutes of mice was recorded individually for each animal immediately after cocaine injection.Results：In acute liver injury model（cocaine 70 mg·kg-1）,the DPPD-pretreated mice exhibited lower lethality rates and significant reductions in the ALT,AST and LDH activities and the content of MDA in a dose dependent manner compared to the cocaine alone mice.Histopathological examination further confirmed the reversal of liver damage induced by cocaine.The DPPD-pretreated mice showed significant reductions in activity counts evoked by cocaine（20 mg·kg-1）.Conclusion：DPPD plays an active role in the prevention of acute mice liver injury and neurotoxicity induced by cocaine.

关 键 词：1 3-二苯-1 3-丙二酮 可卡因 肝毒性 急性肝损伤 神经毒性 

分 类 号：R285.5[医药卫生—中药学]