酒精致大鼠肝损伤早期血清生物标志物水平的变化规律

Changes of Serum Biomarkers levels in Early Stage of Alcohol-induced Liver Injury in Rats

目的:研究酒精性肝损伤的生物标志物谷氨酸脱氢酶(GLDH),α-谷胱甘肽-S-转移酶(α-GST),嘌呤核苷酸磷酸化酶(PNP),精氨酸酶1(Arg1)的动态变化,明确这些指标联合检测是否可以作为酒精性肝损伤早诊断生物标志物。方法:Wistar大鼠48只,随机分为正常组和模型组2组,每组24只,雌雄各半。每日禁食但不禁水7 h后,模型组灌胃50%乙醇/10 mg·kg^-1,正常组灌服同样体积的生理盐水;1 h后按前用量重复灌胃50%乙醇1次,正常组灌服同体积生理盐水,连续造模和给药6 d,造成急性酒精性肝损伤模型。在第2,3,4,6天末次酒精灌胃3 h后,分别随机取2组大鼠每组6只雌雄各半,共12只,处死各组动物,测定天门冬氨酸氨基转移酶(AST),丙氨酸氨基转移酶(ALT),碱性磷酸酶(ALP),胆红素(TBIL),GLDH,α-GST,PNP,Arg1水平。结果:与正常组比较,模型组大鼠ALT,AST,ALP,TBIL,GLDH,PNP,α-GST,Arg1水平差异显著(P <0. 01),表明酒精性肝损伤模型已成功建立。模型组大鼠GLDH,PNP,α-GST,Arg1比ALT,AST水平升高时间早,幅度大。结论:GLDH,PNP,α-GST,Arg1较传统肝功能检测有较强的灵敏性,可以作为酒精性肝损伤早期检测生物标志物。

Objective: To investigate the dynamic changes of the biomarkers of alcoholic liver injury,including glutamate dehydrogenase( GLDH), α-glutathione-S-transferase( α-GST), purine nucleotide phosphorylase( PNP),and arginine enzyme 1( Arg1),and clarify whether these indexes can be used as early diagnostic biomarkers for alcoholic liver injury. Method: 48 Wistar rats were randomly divided into a blank group and a model group,24 rats in each group,half male and half female. After fasting but except water for 7 h,50% ethanol/10 m L·kg-1 was given to the model group by intragastric administration and the same volume of normal saline was administered to the blank group. After 1 h,50% ethanol was again given for once by intragastric administration according to the previous dosage. In the blank group,the same volume of normal saline was administered. After modeling and administration for 6 d,acute alcoholic liver injury model was established. 3 h after the last intragastric administration of alcohol at day 2,3,4,6,six rats( half male and half female) in each group were randomly selected. All the animals were sacrificed to determine the aspartate aminotransferase( AST),alanine aminotransferase( ALT),alkaline phosphatase( ALP),bilirubin( TBIL),GLDH,α-GST,PNP,and Arg1 levels. Result: As compared with the blank group,the levels of ALT,AST,ALP,TBIL,GLDH,PNP,α-GST and Arg1 in the model group were significantly different( P < 0. 01),indicating that the alcoholic liver injury model was successfully established. In the model group,GLDH,PNP,α-GST and Arg1 levels were increased earlier and more significantly than ALT and AST levels. Conclusion: GLDH,PNP,α-GST and Arg1 can be used as biomarkers for early detection of alcoholic liver injury.