| Objective To evaluate the role of phosphatidylinositol-3-kinase/protein kinase B/nuclear factor E2 related factor 2(PI3K/AKT/Nrf2)signaling pathway in resveratrol in reducing myocardial ischemia-reperfusion injury in diabetic rats.Methods Clean male SD rats,aged 2 to 3 months,weighing 240 to 280 g,were injected intraperitoneally with 30 mg/kg streptozotocin(STZ)for 1 week to prepare a diabetes model.Forty diabetic rats were divided into 4 groups(n = 10)according to the random number table method: sham operation group(S group),myocardial ischemia-reperfusion group(I/R group),resveratrol + myocardial deficiency Blood reperfusion group(Res+I/R group),LY294002 + resveratrol + myocardial ischemia-reperfusion group(LY+Res+I/R group).The myocardial ischemia-reperfusion injury model was prepared by ligating the left anterior descending coronary artery for 30 min and reperfusion for 120 min.Res+I/R group and LY+Res+I/R group were intraperitoneally injected with 30 mg/kg resveratrol 1 week before surgery for 7 consecutive days,and LY+Res+I/R group was intraperitoneally injected with 0.5 ml 3 days before surgery LY294002,3 times/d.At 120 min reperfusion,blood samples were taken,and serum CK-MB,LDH levels and serum TNF-?,IL-6 levels were measured by ELISA;ischemic myocardial tissue was taken,myocardial infarct area was detected by TTC method,and myocardial pathology was observed by HE stain Changes,the activity of superoxide dismutase(SOD),the content of glutathione(GSH)and the content of malondialdehyde(MDA)were measured by ELISA method,and AKT,p-AKT,GSK3?,p-GSK3? and Nrf2 expression.Results Compared with I/R group,serum CK-MB,LDH and TNF-?,and IL-6 levels were decreased in Res+I/R group and LY+Res+I/R group(P<0.05);compared with Res+I/R Compared with the R group,the serum levels of CK-MB,LDH and TNF-? and IL-6 in the LY+Res+I/R groupincreased(P<0.05).Compared with I/R group,SOD activity,GSH content increased,and MDA content decreased in Res+I/R group(P<0.05);compared with Res+I/R group,LY+Res+I/R group SOD activity,GSH content,and MDA content increased.Compared with the S group,the expression of p-AKT and p-GSK3? in the I/R group was reduced(P<0.05),and the expression of Nrf2 was increased(P <0.05).Compared with the I/R group,the Res+I/R group,The expressions of p-AKT,p-GSK3?,and Nrf2 all increased(P <0.05);the expressions of p-AKT,p-GSK3?,and Nrf2 were decreased in the LY+Res+I/R group compared with the Res+I/R group(P<0.05).Conclusion The mechanism of resveratrol attenuating myocardial ischemia-reperfusion injury in diabetic rats may be related to activating the PI3K/AKT/Nrf2 signaling pathway and inhibiting oxidative stress and inflammatory responses. |
PDF Full Text Request