复方银杏叶制剂对酒精性肝损伤的防护作用及机制  

Protective effect of compound Ginkgo biloba on alcohol-induced liver injury and its mechanism

作　　者：潘苏华[1] 刘平平[1] 刘亚锋 高青[1] 

机构地区：[1]南京中医药大学药学院江苏省中药药效与安全评价重点实验室,江苏南京210046 [2]郑州澍青医学高等专科学校,河南郑州450064

出　　处：《中国药理学与毒理学杂志》2012年第1期41-46,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：江苏省中医局基金项目(H-024)~~

摘　　要：目的观察银杏叶制剂(CGB)对酒精性肝损伤的防护作用。方法白酒-玉米油混悬液ig给予大鼠造肝损伤模型,连续10周,造模同时分别ig给予银杏叶提取物(GBE)0.8 g·kg-1,CGB 2.4,0.8和0.4 g·kg-1或联苯双酯0.15 g·kg-1。取血测定各组大鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)及肝匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)。并观察肝组织病理及肝细胞线粒体超微结构变化。采用"cocktail"探针药物法测定大鼠ig给予CGB前后血浆中相应的CYP2E1和CYP3A4酶探针氯唑沙宗和氨苯砜的血药浓度,并计算药代动力学参数。通过药代动力学参数的变化,评价CGB对CYP2E1和CYP3A4酶活性的影响。结果连续ig给予乙醇后,大鼠血清转氨酶显著高于正常对照组(P<0.01),与模型组比较,CGB 0.8和2.4 g·kg-1组ALT和AST显著降低(P<0.05);CGB 0.8和2.4 g·kg-1组肝匀浆MDA显著降低、GSH和SOD明显升高(P<0.05)。ig给予CGB前,模型组大鼠氯唑沙宗和氨苯砜的AUC0-24,cmax均较正常对照组显著降低(P<0.05);CGB可使正常大鼠血浆氯唑沙宗和氨苯砜AUC0-24下降(P<0.05),使模型组大鼠血浆氯唑沙宗和氨苯砜的AUC0-24和cmax显著升高(P<0.05)。结论 CGB对酒精性肝损伤有防护作用,其机制与氧化应激干预相关。OBJECTIVE To observe the protective effect of compound Ginkgo biloba（CGB） against alcohol-mediated hepatic injury and its mechanism.METHODS Rats were randomized into seven groups： normal control,model,Ginkgo biloba extract（GBE） 0.8 g·kg-1,CGB 2.4,0.8 and 0.4 g·kg-1,bifendate（Bif） 0.15 g·kg-1 groups.The alcohol-injured hepatic injury model was established after rats were ig given liquor-corn oil suspension for 10 weeks.And CGB,GBE and Bif were ig given in the meantime except normal and model control groups.The content of alamine aminotransferase（ALT） and aspartate aminotransferase（AST） in serum and that of malondialdehyde（MDA）,superoxide dismutase（SOD）,glutathione（GSH） in liver homogenate were measured,so were the hepatic histological and electron microscopy changes in liver mitochondria.Plasma concentrations of chlorzoxazone and DDS were tested before and after CGB was given by the method of ＂cocktail＂,and their pharmacokinetic parameters were calculated to evaluate metabolism activities of cytochrome P-4502E1,CYP2E1 and CYP3A4 indirectly.RESULTS Liver cells were severely damaged by alcohol,resulting in alcoholic hepatitis and the fat liver.Compared with normal control group,the activities of ALT,AST and MDA increased（P0.01） while GSH and SOD decreased（P0.01）.Compared with model group,ALT,AST and MDA obviously decreased（P0.05,P0.01） in CGB 2.4 and 0.8 g·kg-1 groups,while GSH and SOD were significantly increased（P0.05,P0.01）.AUC0-24 and cmax for chlorzoxazone and DDS after CGB was given significantly decreased（P0.05,P0.01） compared to those before CGB was given ig in model groups.CONCLUSION CGB may protect the liver from alcoholic injury and the mechanism may be related to antioxidation.

关 键 词：银杏 植物提取物 酒精性肝疾病 细胞色素P450CYP2E1 细胞色素P450CYP3A4 

分 类 号：R285.5[医药卫生—中药学]