A study on anti-arrhythmia mechanisms of resveratrol on ischemia/reperfusion in rats by regulating PI3K/Akt signaling pathway

Abstract

To investigate whether the phosphatidyl-inositol-3-kinase/protein kinase B(PI3K/Akt)pathway is involved in anti-arrhythmia of resveratrol on ischemia/reperfusion in rat hearts. Forty male rats of normal ECG were randomly divided into 4 groups (n=10):sham control (SC) group, ischemic/reperfusion (I/R) group, resveratrol (Res) group, PI3K inhibitor LY294002 (LY294002) group. The rat myocardial I/R injury model was established in vivo. The arrhythmia and left ventricular functional parameters including left ventricular pressure (LVP), left ventricular systolic pressure (LVSP) and its derivate (±dp/dtmax) were measured; the protein levels of total Akt, phosphorylated Akt and connexin 43 (Cx43) were measured by Western blot; the mRNA level of Cx43 was detected by Real-time PCR. The phosphorylated levels of Akt and myocardial Cx43 were significantly enhanced in Res group as compared with I/R group(P < 0.01); whereas the incidence rate of induced ventricular reperfusion arrhythmias was significantly lower, the left ventricular function was evident-ly enhanced. After addition of PI3K inhibitor LY294002, the protein and mRNA levels of Akt and Cx43 were decreased in LY294002 group, while the incidence rate of reperfusion arrhythmias was significantly higher and the left ventricular function were evidently damaged compared with Res group(P < 0.01). Resveratrol could prevent the occurrence of reperfusion arrhythmias by increasing the content and ac-tivity of myocardial Cx43 through the PI3K/Akt signaling pathway.