8-甲氧补骨脂素对可卡因致小鼠急性肝损伤的保护作用  

Protective effect of 8-methoxypsoralen against cocaine-induced acute hepatic injury in mice

作　　者：魏鹏[1] 刘伟霞[1] 贾凤兰[1] 阮明[1] 张宝旭[1] 

机构地区：[1]北京大学医学部公共卫生学院毒理学系国家中医药管理局中药配伍减毒重点研究室,北京100191

出　　处：《中华中医药杂志》2013年第3期662-665,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家"重大新药创制"科技重大专项(No.2009ZX09103-007)~~

摘　　要：目的:研究8-甲氧补骨脂素(8-MOP)对可卡因(Coc)致小鼠急性肝损伤的保护作用。方法:采用Coc所致小鼠急性肝损伤模型。动物随机分为6组:正常对照组,8-MOP对照组,模型组,8-MOP低、中、高剂量组。正常对照组和模型组给予蒸馏水,8-MOP对照组、8-MOP组给予8-MOP,均为灌胃给药,每天1次,连续4d;最后1次给药30min后,除正常对照组和8-MOP对照组外,其余各组均皮下注射Coc制备小鼠急性肝损伤模型。24h后,检测小鼠血清中丙氨酸氨基转移酶(ALT);留取肝组织,病理染色,光镜观察肝组织病理变化;制备肝匀浆,测定肝组织中还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)和丙二醛(MDA)的含量。结果:与正常对照组比较,模型组小鼠血清中ALT活性明显升高,肝组织出现明显的肝细胞变性坏死;与模型组相比,8-MOP可以明显降低小鼠血清中ALT的活性,降低肝组织中MDA的含量,升高GSH/GSSG比值,肝组织病理损伤也明显减轻。结论:8-MOP对Coc致小鼠急性肝损伤具有明显的保护作用。Objective： To investigate the hepatoprotective effect of 8-methoxypsoralen against cocaine-induced acute hepatic injury in mice. Methods： Liver injury model of mice was induced by subcutaneous injection of cocaine. The mice were randomly divided into 6 groups： normal control group, 8-methoxypsoralen control group, positive control group and three 8-methoxypsoralen groups. The normal control group and positive control group received gastric gavage of water, three 8-methoxypsoralen groups and 8-methoxypsoralen control group were given 8-methoxypsoralen by gastric gavage for 4 consecutive days, once per day. Thirty minutes after last administration, the mice in other groups received cocaine to induce acute hepatic injury, except the normal control group and 8-methoxypsoralen control group. 24 hours later, the activity of serum alanine aminotransferase （ALT） was determined, and the liver tissues were collected for histopathological assessment under light microscope. The ratio of glutathione （GSH） and oxidized glutathione （GSSG）, and the content of GSH, GSSG and malondialdehyde （MDA） in liver homogenate were also measured. Results： Compared with the normal control group, the model group could markedly increase serum ALT activity, and the degeneration and necrosis could be observed in liver tissues. Compared with the model group, 8-methoxypsoralen could markedly decrease serum ALT activity, reduce the MDA level in liver homogenate, and increase GSH content and the ratio of GSH/GSSG in the liver homogenate. The hepatic histopathological changes in liver were also significantly ameliorated. Conclusion： The 8-methoxypsoralen can prevent the liver from cocaineinduced acute hepatic injury.

关 键 词：8-甲氧补骨脂素 可卡因 急性肝损伤 保护作用 

分 类 号：R965[医药卫生—药理学]