{"title":"Role of PI3K/Akt/Nrf2 signaling pathway in resveratrol preconditioning-induced cardioprotection in diabetic rats","authors":"Guiping Xu, Juan-juan Fu, Xuan Zhao, Xiaoli Wang","doi":"10.3760/CMA.J.ISSN.0254-1416.2019.10.011","DOIUrl":null,"url":null,"abstract":"Objective \nTo evaluate the role of phosphatidylinositol-3-kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 (PI3K/Akt/Nrf2) signaling pathway in resveratrol preconditioning-induced cardioprotection in diabetic rats. \n \n \nMethods \nClean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-280 g, were used in the study.The diabetes model was established by intraperitoneal injection of streptozotocin 30 mg/kg once a day for 7 consecutive days.Forty diabetic rats were selected and divided into 4 groups (n=10 each) according to the random number table method: sham operation group (S group), myocardial ischemia-reperfusion (I/R) group (I/R group), resveratrol plus myocardial I/R group (Res+ I/R group), and PI3K inhibitor LY294002 plus resveratrol plus myocardial I/R group (LY+ Res+ I/R group). The myocardial I/R injury model was established by ligating the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized rats.Resveratrol 20 mg/kg was intraperitoneally injected once a day for 7 consecutive days at one week before surgery in Res+ I/R and LY+ Res+ I/R groups.LY294002 1.5 mg/kg was intraperitoneally injected at 30 min before operation in LY+ Res+ I/R group.After 120 min of reperfusion, blood samples were taken for determination of serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) concentrations (by enzyme-linked immunosorbent assay), and myocardial tissues at the ischemic area were obtained for determination of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA)levels (by enzyme-linked immunosorbent assay) and expression of Akt, phosphorylated Akt (p-Akt), glycogen synthase kinase 3β (GSK3β), phosphorylated GSK3β (p-GSK3β) and Nrf2 (by Western blot). \n \n \nResults \nCompared with group S, serum CK-MB and LDH concentrations were significantly increased, the SOD and GSH levels were decreased, the MDA level was increased, and the expression of p-Akt and p-GSK3β was down-regulated in I/R group (P<0.05). Compared with I/R group, serum CK-MB and LDH concentrations were significantly decreased, the SOD and GSH levels were increased, the MDA level was decreased, and the expression of p-Akt, p-GSK3β and Nrf2 was up-regulated in Res+ I/R group (P<0.05). Compared with Res+ I/R group, serum CK-MB and LDH concentrations were significantly increased, the SOD and GSH levels were decreased, the MDA level was increased, and the expression of p-Akt, p-GSK3β and Nrf2 was down-regulated in LY+ Res+ I/R group (P<0.05). \n \n \nConclusion \nThe mechanism of resveratrol preconditioning-induced cardioprotection is related to activating PI3K/Akt/Nrf2 signaling pathway and inhibiting oxidative stress responses in diabetic rats. \n \n \nKey words: \nMyocardial reperfusion injury; Diabetes mellitus; Phenols; 1-phosphatidylinositol 3-kinase; Protein-serine-threonine kinases; NF-E2-related factor 2","PeriodicalId":10053,"journal":{"name":"中华麻醉学杂志","volume":"39 1","pages":"1189-1193"},"PeriodicalIF":0.0000,"publicationDate":"2019-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"中华麻醉学杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3760/CMA.J.ISSN.0254-1416.2019.10.011","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
To evaluate the role of phosphatidylinositol-3-kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 (PI3K/Akt/Nrf2) signaling pathway in resveratrol preconditioning-induced cardioprotection in diabetic rats.
Methods
Clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-280 g, were used in the study.The diabetes model was established by intraperitoneal injection of streptozotocin 30 mg/kg once a day for 7 consecutive days.Forty diabetic rats were selected and divided into 4 groups (n=10 each) according to the random number table method: sham operation group (S group), myocardial ischemia-reperfusion (I/R) group (I/R group), resveratrol plus myocardial I/R group (Res+ I/R group), and PI3K inhibitor LY294002 plus resveratrol plus myocardial I/R group (LY+ Res+ I/R group). The myocardial I/R injury model was established by ligating the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized rats.Resveratrol 20 mg/kg was intraperitoneally injected once a day for 7 consecutive days at one week before surgery in Res+ I/R and LY+ Res+ I/R groups.LY294002 1.5 mg/kg was intraperitoneally injected at 30 min before operation in LY+ Res+ I/R group.After 120 min of reperfusion, blood samples were taken for determination of serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) concentrations (by enzyme-linked immunosorbent assay), and myocardial tissues at the ischemic area were obtained for determination of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA)levels (by enzyme-linked immunosorbent assay) and expression of Akt, phosphorylated Akt (p-Akt), glycogen synthase kinase 3β (GSK3β), phosphorylated GSK3β (p-GSK3β) and Nrf2 (by Western blot).
Results
Compared with group S, serum CK-MB and LDH concentrations were significantly increased, the SOD and GSH levels were decreased, the MDA level was increased, and the expression of p-Akt and p-GSK3β was down-regulated in I/R group (P<0.05). Compared with I/R group, serum CK-MB and LDH concentrations were significantly decreased, the SOD and GSH levels were increased, the MDA level was decreased, and the expression of p-Akt, p-GSK3β and Nrf2 was up-regulated in Res+ I/R group (P<0.05). Compared with Res+ I/R group, serum CK-MB and LDH concentrations were significantly increased, the SOD and GSH levels were decreased, the MDA level was increased, and the expression of p-Akt, p-GSK3β and Nrf2 was down-regulated in LY+ Res+ I/R group (P<0.05).
Conclusion
The mechanism of resveratrol preconditioning-induced cardioprotection is related to activating PI3K/Akt/Nrf2 signaling pathway and inhibiting oxidative stress responses in diabetic rats.
Key words:
Myocardial reperfusion injury; Diabetes mellitus; Phenols; 1-phosphatidylinositol 3-kinase; Protein-serine-threonine kinases; NF-E2-related factor 2