丙泊酚对肝脏缺血再灌注中线粒体功能和氧化应激的影响  

Study on the Protective Mechanism of Propofol on Mitochondrial Function and Oxidative Stress in Hepatic Ischemia-reperfusion Injury

作　　者：夏乐强[1] 张先杰[1] 刘欣[1] 王瑛[1] 高红强[2] XIA Leqiang;ZHANG Xianjie;LIU Xin;WANG Ying;GAO Hongqiang(Department of Anesthesiology,People's Hospital of Deyang City,Deyang618000,China;Department of Hepatobiliary Surgery,the First Hospital of Kunming,Kunming650000,China)

机构地区：[1]德阳市人民医院麻醉科,德阳618000 [2]云南省昆明市第一人民医院肝胆外科,昆明650000

出　　处：《宁夏医科大学学报》2020年第6期590-596,共7页Journal of Ningxia Medical University

基　　金：云南省科技厅高校联合面上项目(2018FH001-072)。

摘　　要：目的探究丙泊酚对于肝脏缺血再灌注中线粒体功能和氧化应激的影响。方法将雄性Wistar大鼠随机分为6组:替来他明处理的假手术(SHAM)与肝脏缺血再灌注(I/R)大鼠;七氟醚处理的SHAM与I/R大鼠;丙泊酚处理的SHAM与I/R大鼠。分别检测6组中线粒体功能与氧化应激。采用Western blot检测缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)蛋白表达。结果 I/R大鼠线粒体氧气摄取、呼吸活性、膜电位以及质子漏发生变化,丙泊酚可以抑制这些变化,七氟醚则没有此作用。丙泊酚可以抑制I/R大鼠中H2O2产生,自由基漏和羟基壬烯酸蛋白加和物产生。丙泊酚处理I/R大鼠后ATP稳态得到较好恢复。丙泊酚麻醉I/R大鼠可抑制HIF-1α蛋白表达以及相关靶基因TfR、HO-1表达(P均<0.05)。结论丙泊酚可以降低肝脏I/R所造成的线粒体损伤,能够保护呼吸链并降低ATP损耗以及质子漏,这种保护作用可能涉及HIF-1α信号通路。Objective To explore the protective effect of propofol on mitochondrial dysfunction and oxidative stress in liver ischemia/reperfusion. Methods Male wistar rats were randomly divided into six groups: SHAM group and I/R group anaesthetized by tiletamine/zolazepam(CTRL);SHAM group and I/R group anesthetized by propofol administered in the femoral vein(PROP);SHAM group and I/R group anaesthetized with inhaled2%sevoflurane(SEVO).We compared different anesthetics on mitochondria function and oxidative stress. Western blot was used to determine the expression of hypoxia-inducible factor-1α(HIF-1α). Results Mitochondrial oxygen uptake,respiratory activity,membrane potential and proton leak were altered in liver of I/R rats,and this alteration was inhibited by administration with propofol but not sevoflurane. Propofol could inhibit the production of H2O2,free radical leakage and the production of hydroxynonaenoic acid protein adduct in I/R rats.I/R group anesthetized by propofol showed a better recovery of hepatic ATP homeostasis. Anesthetizing with propofol reduced protein expression of HIF-1α and its target genes including Tf R and HO-1. Conclusion Propofol can reduce mitochondrial damage caused by liver ischemia-reperfusion,protect the respiratory chain and reduce ATP loss and proton leakage. This protection may involve the HIF-1α signaling pathway.

关 键 词：丙泊酚 线粒体 氧化应激 肝脏缺血再灌注 

分 类 号：R971.2[医药卫生—药品]