短期饥饿加重异烟肼引起的小鼠肝脏氧化应激  

A short term of starvation aggravates isoniazid-induced oxidative stress in mouse liver

作　　者：段自皞[1] 于涛[1] 张程[1] 陈熙[2] 张莹[1] 徐娟[2] 许建明[2] 魏伟[3] 徐德祥[1] 

机构地区：[1]安徽医科大学卫生毒理学系,合肥230032 [2]安徽医科大学第一附属医院消化内科,合肥230022 [3]安徽医科大学临床药理研究所,合肥230032

出　　处：《安徽医科大学学报》2010年第4期447-450,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:30371667;30572223);安徽省自然科学基金(编号:090413142)

摘　　要：目的研究短期饥饿是否加重异烟肼(INH)引起的小鼠肝脏氧化应激效应。方法实验小鼠分为4组:对照组和INH组经灌胃分别给予生理盐水和INH(100mg/kg);饥饿组及饥饿+INH组分别在给予生理盐水和INH前12h及后6h均禁食。所有小鼠均连续处理4d,在末次INH处理后6h取材。取血清用于生化指标检测,用Griffith法检测肝脏还原型谷胱甘肽(GSH)水平,比色法检测肝脏羰基产物丙二醛含量。用蛋白质免疫印迹技术检测肝脏CYP2E1蛋白水平,用RT-PCR技术检测肝脏CYP2E1 mRNA水平。结果 INH组小鼠血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、总胆汁酸及病理学检查均未发现明显的改变。进一步的研究发现,短期饥饿或INH单独处理均显著上调小鼠肝脏CYP2E1蛋白水平,但对Cyp2e1 mRNA水平均无明显影响;与INH组小鼠相比,短期饥饿显著降低INH引起的小鼠肝脏GSH消耗并明显升高INH引起的脂质过氧化水平。结论短期饥饿加重INH引起的小鼠肝脏氧化应激至少部分经上调肝脏CYP2E1蛋白表达所介导。Objective To investigate whether a short term of starvation aggravates isoniazid（INH）-induced oxidative stress in mouse liver.Methods Mice were divided into four groups：mice were respectively administered with saline and INH（100 mg/kg）for four consecutive days in control and INH alone group;in starvation and INH plus starvation group,mice were starved for 12 h before INH and 6 h after INH treatment.Mice were sacrificed 6 h after the last INH treatment.Sera were collected for measurements of biochemical parameters.The hepatic glutathione（GSH）of mice was determined by the method of Griffith and lipid peroxidation was quantified by measuring malondialdehyde（MDA）.The CYP2E1 protein level was detected by Western blot and Cyp2e1 mRNA level was detected by RT-PCR.Results We found that INH administration（100 mg/kg）daily by gavage for four days did not induce any histological damage in mouse liver.In addition,no significant difference on serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total bilirubin and total bile acid was observed among different groups.Compared with control group mice,either INH treatment or a short term of starvation resulted in the decreased hepatic GSH level and the elevated liver lipid peroxidation level.Furthermore,a short term of starvation or INH treatment significantly upregulated CYP2E1 protein level,but had no effect on Cyp2e1 mRNA level in mouse liver.Compared with INH alone group,a short term of starvation significantly aggravated INH-induced upregulation of CYP2E1 in mouse liver.Conclusion A short term of starvation aggravates INH-induced oxidative stress in mouse liver.Hepatic CYP2E1 upregulation,induced by a short term of starvation,contributes,at least partially,to INH-induced hepatic oxidative stress in starved mice.

关 键 词：异烟肼 氧化性应激 饥饿 谷胱甘肽 

分 类 号：R978.3[医药卫生—药品] R151.1[医药卫生—药学]