吴茱萸致大鼠和小鼠肝损伤血清酶生物标志物变化的研究  

Research on Changes of Serum Enzyme Biomakers in Mice and Rats with Liver Injury Caused by Fructus Euodiae

作　　者：周璐[1] 徐婷婷[1] 金若敏[1] 乔靖怡[1] 姚广涛[1] 

机构地区：[1]上海中医药大学药物安全评价研究中心,上海201203

出　　处：《中药新药与临床药理》2014年第4期418-423,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家重点基础研究发展计划(973计划)项目(2009CB522807);国家科技重大专项项目(2009ZX09502-002);国家科技重大专项课题(2011ZX09301-009)

摘　　要：目的探索酶学生物标志物精氨酸酶玉(Arginase玉,Arg玉)、琢-谷胱甘肽S转移酶(琢-glutathione-S-transferase,琢-GST)、谷胱苷肽脱氢酶(Glutamic dehydrogenase,GLDH)和嘌呤核苷磷酸酶(purine nucleosidephosphorlyase,PNP)作为吴茱萸致肝损伤早期敏感指标的可能性。方法取KM小鼠,随机分为正常组和吴茱萸组,吴茱萸组连续28 d灌胃给予吴茱萸30 g·kg-1·d-1,正常组灌服等体积蒸馏水;取Wistar大鼠,随机分为正常组和吴茱萸组,吴茱萸组连续28 d灌胃给予吴茱萸20 g·kg-1·d-1,正常组灌服等体积蒸馏水,各组均于给药后不同时间点取血及肝组织。全自动生化分析仪检测动物血清生化指标:丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和总胆红素(TB)含量,ELISA法检测血清中Arg玉、琢-GST、GLDH和PNP的含量。HE染色,光镜观察肝组织病理形态学变化。结果小鼠实验中,与同时间点对照组相比,吴茱萸组ALT于给药21 d和28 d显著性升高(P约0.05或P约0.01),肝组织形态学检查仅见个别小鼠的肝细胞坏死。吴茱萸组血清生物标志物Arg玉、琢-GST和PNP于7 d起明显升高,GLDH于14 d起明显升高(P约0.05或P约0.01),均持续至28 d。大鼠实验中,与同时间点正常组比较,吴茱萸组常规生化指标均无明显变化,肝组织形态学检查仅极少数动物见肝细胞坏死,吴茱萸组血清生物标志物Arg玉、GLDH和PNP于7 d起明显升高,琢-GST于14 d起明显升高(P约0.05,P约0.01),均持续至28 d。结论血清Arg玉、琢-GST、GLDH和PNP可作为吴茱萸致肝损伤的早期敏感酶学生物标志物。Objective To investigate the possibility of taking serum enzyme biomarkers of arginase I （Arg I ）, α-glutathione-S-transferase（ α-CST）, glutamie dehydrogenase（GLDH） and purine nucleoside phosphorlyase（PNP） as the early sensitive indexes of liver injury caused by the decoction of Fructus Euodiae. Methods KM mice were randomly divided into Fructus Euodiae group and normal control group, which were administrated respectively with Euodiae Fructus decoction at the dose of 30g crude drug/kg daily or equal volume of distilled water by gavage for consecutive 28 days. At the same time, Wistar rats were also randomly divided into Fructus Euodiae group and normal control group, which were administrated respectively with Euodiae Fructus decoction at the dose of 20 g crude drug/kg daily or equal volume of distilled water by garage for consecutive 28 days. Blood samples and liver tissue were taken from the mice and rats at different time points. The activities of serum alanine aminotransferase（ALT） , aspartate aminotransferase（AST） and the concentration of total bilirubin（TB）were determined by automatic biochemical analyzer. The contents of serum Arg-Ⅰ, α-GST, GLDH and PNP were detected by ELISA. Liver tissue was stained by HE, and then the hepatic pathological changes were observed under light microscope. Results In mice experiment, the activity of ALT was significantly increased on day 21 and 28 （P〈 0.01 compared with that in the control group） in Fructus Euodiae group. Histological examination showed that few mice developed into focal liver cell necrosis. The contents of serum Arg-Ⅰ, α-GST and PNP were increased obviously from day 7 and the content of serum GLDH was increased obviously from day 14 in Fructus Euodiae group（P 〈 0.05 or P 〈 0.01 ）, and the changes of Arg-Ⅰ,α-GST, GLDH and PNP continued till day 28. In rat experiment, the activities of ALT, AST and the concentration of TB showed no obvious changes. Focal liver cell necrosis could be observed occasionally in t

关 键 词：吴茱萸 大鼠 小鼠 肝损伤 生物标志物 

分 类 号：R285.5[医药卫生—中药学]