白藜芦醇后处理通过PI3K/Akt/Nfr2上调HO-1对大鼠心肌I/R的保护研究  

Study on protective effect of resveratrol post-treament on rat myocardial I/R injury through up-regulating HO-1 via PI3K/Akt/Nfr2

作　　者：邓颖[1] 张雄[2] 胡红 DENG Ying;ZHANG Xiong;HU Hong(Department of Cardiology,First Branch Hospital of First Affilliated Hospital,Chongqing Medical University,Chongqing 400011,China;Research Institute of Neuroscience,Chongqing Medical University,Chongqing 400016,China;Department of Nephrology,First Branch Hospital of First Affilliated Hospital,Chongqing Medical University,Chongqing 400011,China)

机构地区：[1]重庆医科大学附属第一医院第一分院心内科,400011 [2]重庆医科大学神经科学研究中心,400016 [3]重庆医科大学附属第一医院第一分院肾内科,400011

出　　处：《重庆医学》2018年第9期1176-1178,1182,共4页Chongqing medicine

摘　　要：目的观察白藜芦醇对大鼠心肌缺血/再灌注损伤(I/R)的作用并探讨其可能的机制。方法选用60只雄性SD大鼠,分为假手术组、I/R组、I/R+白藜芦醇组(I/R+Res组)、I/R+白藜芦醇+LY294002组(I/R+Res+LY组)。采用结扎SD大鼠冠状动脉左前降支30min,然后再灌注2h的方法构建大鼠心肌I/R损伤模型,并于再灌注前1min由舌下静脉推注白藜芦醇(20mg/kg)或LY294002(5mg/kg)。检测各组大鼠血浆和心肌组织中丙二醛(MDA)和超氧化物歧化酶(SOD)水平以及心肌组织中血红素加氧酶-1(HO-1)水平,Western blot法检测心肌组织中的PI3K、Akt(p-Akt)、Nrf2、HO-1蛋白表达变化水平。结果与I/R组比较,I/R+Res组大鼠血浆和心肌中MDA的水平降低,SOD的活性水平升高;HO-1的活性和表达增强(P<0.05)。I/R+Res组心肌组织中PI3K、Akt(p-Akt)、Nrf2、HO-1蛋白的表达水平与I/R组比较升高(P<0.05)。而在I/R+Res+LY组,这些作用可被PI3K/Akt抑制剂LY294002所部分消除。结论白藜芦醇后处理可通过上调PI3K/Akt/Nfr 2活性,进而增强HO-1蛋白的活性和表达,从而发挥HO-1抗氧化作用,减轻心肌的缺血再灌注损伤。Objective To observe the effect of resveratrol(Res)on myocardial ischemia/reperfusion(I/R)injury in rats and to explore its potential mechanisms.Methods Sixty male SD rats were selected and divided into the sham operation group,I/R group,I/R+Res group and I/R+Res+LY294002(I/R+Res+LY)group.The rat myocardial I/R injury model was established by the ligation of left anterior descending coronary artery for 30 min and then by reperfusion for 2 h,and the injection of Res(20 mg/kg)or LY294002(5 mg/kg)was given via sublingual vein at 1 min before reperfusion.The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in plasma and myocardial tissue,and level of heme oxygenase 1(HO-1)in myocardial tissues were determined in each group;Western blot was used to detect the expression level change of PI3K,Akt(p-Akt),Nrf2 and HO-1 protein in myocardial tissue.Results Compared with the I/R group,the plasma and myocardial MDA levels in I/R+Res group were reduced,the SOD activity level was elevated,and the activity and expression of HO-1 was enhanced(P<0.05);compared with the I/R gourp,the expression levels of PI3K,Akt(p-Akt),nrf2 and HO-1 protein levels in myocardial tissue of I/R+Res group were increased(P<0.05).But these effects in the I/R+Res+LY group could be partially eliminated by PI3K/Akt inhibitor LY294002.Conclusion Resveratrol post-treatment can enhance the activity and expression of HO-1 protein through up-regulating the activity of PI3K/Akt/Nfr2,and then promotes the activity and expression of HO-1,thus plays the HO-1 anti-oxidative role,and alleviates myocardial I/R injury.

关 键 词：白藜芦醇 心肌缺血 再灌注损伤 血红素加氧酶-1 PI3K/Akt/Nfr2 大鼠 Sprague-Dawley 

分 类 号：R969[医药卫生—药理学]