瑞芬太尼通过核因子E2相关因子通路增强自噬改善大鼠心肌缺血再灌注损伤的研究  

Remifentanil against myocardial ischemia-reperfusion injury by enhancing autophagy via the activation of nuclear factor erythroid2-related factor 2 pathway in rat model

作　　者：陈中青 侯丹丹 王伟[2] CHEN Zhong-qing;HOU Dan-dan;WANG Wei(The Cadre Ward of Heart Center,General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia Hui Autonomous Region,China;Department of Neurosurgery,General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia Hui Autonomous Region,China)

机构地区：[1]宁夏医科大学总医院心脏中心干部病房,宁夏回族自治区银川750004 [2]宁夏医科大学总医院神经外科,宁夏回族自治区银川750004

出　　处：《中国临床药理学杂志》2023年第1期47-51,共5页The Chinese Journal of Clinical Pharmacology

基　　金：宁夏自然科学基金资助项目(2020AAC03365)。

摘　　要：目的探索瑞芬太尼后处理对心肌缺血再灌注(IR)损伤保护作用的机制。方法用结扎大鼠冠状动脉左前降支的方法建立心肌IR损伤模型。将成年雄性SD大鼠随机分为假手术组、模型组和实验组。假手术组只穿线不结扎;模型组,缺血30 min,再灌注30 min;实验组从大鼠缺血25 min至再灌注前5 min,连续输注瑞芬太尼10μg·kg^(-1)·min^(-1)。用试剂盒法检测丙二醛(MDA)水平、超氧化物歧化酶(SOD)活性和谷胱甘肽/L-谷胱甘肽(氧化)(GSH/GSSG)的含量,用实时荧光定量聚合酶链反应检测Nrf2、血红素氧化酶1(HO-1)、NAD(P)H:醌氧化还原酶1(NQO1)的变化。结果实验组、模型组与假手术组的MDA浓度分别为(4.61±2.04),(8.02±2.12)和(3.78±1.63)nmol·mg^(-1),SOD活性分别为(86.49±15.53),(60.43±24.71)和(100.42±16.47)U·mg^(-1),GSH/GSSG比值分别为8.23±3.68,2.59±0.88和9.21±4.08,Nrf2表达水平分别为3.11±0.78,2.08±1.06和1.00±0.09,HO-1表达水平分别为3.29±1.20,2.23±0.87和1.00±0.09,NQO1表达水平分别为3.35±1.08,2.29±0.94和1.00±0.12。实验组的上述指标与模型组比较,差异均有统计学意义(P<0.05或P<0.01)。结论瑞芬太尼后处理可能通过Nrf2通路激活自噬,保护心肌IR损伤。Objective To investigate the protective mechanism of remifentanil postconditioning(RPC)against myocardial ischemia/reperfusion(IR)injury.Methods The anterior descending branch of the left anterir descending(LAD)was ligated to establish myocardial IR injury model.Healthy adult male SD rats were randomly divided into sham group,model group and experimental group.Rats in sham group underwent the same surgical procedure without coronary artery ligation.In model group,the rats only were ligated at LAD for 30 min and then recirculation for 30 min.Animals in experimental group were achieved by continuous infusion of remifentanil 10μg·kg^(-1)·min^(-1) from 25 min of ischemia to the first 5 min of reperfusion.The malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione/L-glutathione(oxidized)ratio(GSH/GSSG)were measured by commercial kits.The biomarker of the Nrf2,heme oxygenase 1(HO-1),NAD(P)H:quinone oxidoreductase(NQO1)were measured by quantitative real-time polymerase chain reaction.Results The levels of malondialdehyde in experimental group,model group and sham group were(4.61±2.04),(8.02±2.12)and(3.78±1.63)nmol·mg-1;superoxide dismutase activities were(86.49±15.53),(60.43±24.71)and(100.42±16.47)U·mg^(-1);the GSH/GSSG ratios were 8.23±3.68,2.59±0.88 and 9.21±4.08;the expression levels of Nrf2 were 3.11±0.78,2.08±1.06 and 1.00±0.09;the expression levels of HO-1 were 3.29±1.20,2.23±0.87 and 1.00±0.09;the expression levels of NQO1 were 3.35±1.08,2.29±0.94 and 1.00±0.12.Compared with model group and experimental group,the above indexes were statistical significant(P<0.05,P<0.01).Conclusion These findings suggest that RPC may protect myocardial IR injury via activation of Nrf2pathway.

关 键 词：瑞芬太尼后处理 心肌缺血/再灌注 自噬 核因子E2相关因子 

分 类 号：R971.2[医药卫生—药品]