白藜芦醇后处理对大鼠心肌缺血／再灌注损伤的保护作用及机制研究

Protective effect of resveratrol post - treament on myocardial ischemia/ reperfusion injury of the rats

目的观察白藜芦醇后处理对SD大鼠的心肌缺血/再灌注（I/R）损伤的保护作用 并探讨其机制。方法选用80只SD雄性大鼠，随机分为假手术组、I/R组、I/R ＋白藜芦醇（20 mg/kg）组和I/R ＋白藜芦醇＋ LY294002（5 mg/kg）组。采用结扎SD大鼠左冠状动脉的前降支30 min,再灌注2 h的方法构建心肌I/R损伤模型，在再灌注前1 min由舌下静脉推注白藜芦醇或 LY294002。首先TTC法检测各组心肌组织的梗死面积;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）含量以及心肌组织中血红素加氧酶-1 （heme oxygenase - 1， HO -1）的含量，最后用Western blot法检测心肌组织中的PI3K、P - Akt、Nrf2、HO - 1蛋白表达变 化水平。结果与I/R组比较，白藜芦醇后处理可明显降低心肌梗死面积，也可降低血浆中MDA 含量，升高SOD活性水平,可增强H0-1活性（P 〈0.05），进一步显示白藜芦醇增加了 I/R大鼠 心肌组织中PI3K、P-Akt、Nfr2、H0-1蛋白的表达水平（/5〈0.05），其作用又可被PI3K/Akt抑制 剂LY294002部分消除。结论白藜芦醇后处理对I/R后的心肌组织有保护作用，其机制可能与 白藜芦醇上调PI3K/Akt/Nfr2的活性，进而增强HO - 1蛋白的活性和表达，从而发挥其抗氧化作 用有关。

Objective To observe the protective effects of resveratrol on myocardial ischemia/ reperfusion （I/R） injury in SD rats and to explore the potential mechanisms. Methods 80 male SD rats were randomly divided into four groups： sham operation group, I/R group, I/R ＋ resveratrol group （20 mg/kg） , I/R ＋ resveratrol ＋ LY294002 （5 mg/kg）. For establishment of myocardial I/R injury animal models, left anterior descending coronary artery was ligated for 30 min followed by reperfusion for 2 h, and injection of resveratrol （20 mg/kg） or LY294002 （ 5 mg/kg） before reperfusion 1 min via sublingual vein. TTC staining was for assessing the infarction areas of myocardium. Blood samples and myocardial tissues were collected for detecting the concentration of malondialdehyde （ MDA ） and superoxide dismutase （ SOD） ; meanwhile, the activity of heme oxygenase - 1 （ HO - 1 ） was determined; Western blot was used to detect the expression of of PI3K, p - Akt, Nrf2 and HO - 1 at protein level in the myocardial tissue. Results Compared to the 1/R group, resveratrol post - treatmentremarkably decreased the infarction areas of myocardium induced by I/R injury; and significantly reduced the concentration of MDA; but, notably increased the concentration of SOD; meanwhile, resveratrol enhanced the activity of HO -1 （P 〈0.05） ; furthermore, the expression of PI3K, p- Akt, Nrf2 and HO - 1 at protein levels were all increased after resveratrol post - treatment （ P 〈 0.05 ）, which were partly eliminated by PI3K/Akt inhibitor LY294002. Conclusion Resveratrol post - treatment plays protective roles on myocardium induced by I/R injury in SD rats, the mechanisms may be correlated with that resveratrol increased the activity and expression of HO - 1 through up - regulating the activity of PI3K/Akt/Nfr2, and then plays the anti - oxidative role of HO - 1.