Role of PI3K/Akt/Nrf2 signaling pathway in resveratrol preconditioning-induced cardioprotection in diabetic rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of phosphatidylinositol-3-kinase/protein kinase B/nucle-ar factor erythroid 2-related factor 2(PI3K/Akt/Nrf2)signaling pathway in resveratrol preconditioning-in-duced 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 intraper-itoneal injection of streptozotocin 30 mg/kg once a day for 7 consecutive days.Forty diabetic rats were se-lected and divided into 4 groups(n＝10 each)according to the random number table method: sham opera-tion group(S group),myocardial ischemia-reperfusion(I/R)group(I/R group),resveratrol plus myo-cardial 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 immu-nosorbent 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 immu-nosorbent 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-regu-lated in I/R group(P＜0.05).Compared with I/R group,serum CK-MB and LDH concentrations were sig-nificantly decreased,the SOD and GSH levels were increased,the MDA level was decreased,and the ex-pression 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 precondi-tioning-induced cardioprotection is related to activating PI3K/Akt/Nrf2 signaling pathway and inhibiting oxi-dative stress responses in diabetic rats.