全反式维A酸对大鼠肝脏缺血再灌注损伤肝组织锰超氧化物歧化酶的影响  

All-trans retinoic acid increases hepatic manganese superoxide dismutase in liver ischemia/reperfusion injury in rats

作　　者：饶建华[1] 姜新春[1] 孟凡军[1] 齐敦峰 李欢送[1] 刘养岁[1] 张昕辉[1] 

机构地区：[1]徐州市中心医院普外科,江苏省213000

出　　处：《中华临床医师杂志（电子版）》2011年第10期2906-2910,共5页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：目的探讨全反式维A酸对大鼠肝脏缺血再灌损伤时肝脏组织锰超氧化物歧化酶(MnSOD)的影响。方法将18只雄性Sprague-Dawley(SD)大鼠随机分成3组(每组6只):假手术组、对照组、实验组。实验组腹腔注射全反式维A酸15mg.kg-1.d-1,对照组腹腔注射同体积中介液二甲基亚砜(DMSO),共14d。建立肝脏70%缺血再灌注模型,缺血1h复流24h后采集各组大鼠肝脏和血清,测定血清中ALT和AST,HE染色光镜下观察肝组织的变化;采用比色法检查肝组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)的活性;Western blot和实时RT-PCR检测MnSOD蛋白含量和mRNA表达。结果相对于对照组,全反式维A酸能明显降低缺血再灌注后血清ALT水平[(138.61±54.63)U/Lvs.(458.53±83.17)U/L,P=0.001)]和AST水平[(355.57±70.92)U/Lvs.(1152.48±135.86)U/L,P=0.001)];明显改善缺血再灌注引起的肝脏组织学损伤;明显降低MDA的活性[(0.47±0.03)nmol/mgvs.(0.77±0.04)nmol/mg,P=0.001)],增加SOD的活性[(221.36±14.18)U/mgvs.(158.01±13.17)U/mg,P=0.001)];增加肝脏缺血再灌注后MnSOD的蛋白水平和MnSOD mRNA的表达(1.39±0.22vs.0.40±0.07,P=0.001)。结论全反式维A酸可以明显增加缺血再灌注时肝组织MnSOD表达,增加SOD的活性,减少细胞脂质过氧化,降低MDA的水平,从而减轻肝脏缺血再灌注损伤。Objective To investigate the effects of all-trans retinoic acid(ATRA) on manganese superoxide dismutase(MnSOD) during ischemia/reperfusion injury in rats.Methods 18 male Sprague-Dawley rats were randomized into three groups(6/group).Sham group:sham operation + no treatment;control group:liver I/R + medium(DMSO for 14 days),experimental group:liver I/R + ATRA treatment(15 mg·kg-1·d-1 for 14 days).Partial(70% volume) hepatic ischemia was established for 1 hour,followed by 24 h of reperfusion,and collected sample of liver tissue and serum.Alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were measured in serum.Hepatic pathology was evaluated by hematoxylin and eosin(HE).Content of malondialdehyde(MDA) and superoxide dismutase(SOD) activity were analyzed by colorimetry.Western blot and real-time RT-PCR were used to assess the expression of manganese superoxide dismutase(MnSOD) protein and mRNA.Results Compared with the sham group,ATRA significantly decreased the levels of ALT [(138.61±54.63)U/L vs.(458.53±83.17)U/L,P=0.001]and AST[(355.57±70.92)U/L vs.(1152.48±135.86)U/L,P=0.001],improved hepatic pathological damage,reduced the activity of MDA[(0.47±0.03)nmol/mg vs.(0.77±0.04)nmol/mg,P=0.001],up-regulated the activity of SOD[(221.36±14.18)U/mg vs.(158.01±13.17)U/mg,Conclusions ATRA can significantly alleviate hepatic ischemia/reperfusion injury by increasing expression of MnSOD to increase the activity of SOD,reduce lipid peroxidation and the level of MDA.

关 键 词：肝 再灌注损伤 维A酸 超氧化物歧化酶 

分 类 号：R965[医药卫生—药理学]