Ticagrelor reduces myocardial cell injury induced by myocardial ischemia-reperfusion in diabetic rats by activating JAK2/STAT3.

The treatment of diabetic patients with myocardial infarction is still full of challenges. Diabetes may exacerbate myocardial ischemia/reperfusion (I/R) injury. Ticagrelor alleviates I/R injury. However, the protective effects of ticagrelor on the diabetic myocardium following I/R and the underlying molecular mechanism remain unclear. In this study, diabetic rats were induced by STZ, and the I/R injury model was established by ligation of coronary arteries. The rats have then treated with 300mg/kg/d of ticagrelor with or without 5mg/kg of Protein Kinase C (PKC) inhibitor chelerythrine (Che) for 14 days. Then the myocardial tissue was collected, the area of myocardial infarction was significantly reduced after treatment with ticagrelor after staining with triphenyl tetrazolium chloride and HE. Ticagrelor also inhibited I/R-induced cardiomyocyte pyroptosis, apoptosis and reduced oxidative stress levels, while Che partially weakened the myocardial protective effect of ticagrelor. In the Oxygen Glucose Deprivation (OGD) model of H9c2 cells, it was found that ticagrelor reduced OGD-induced apoptosis of H9c2 cells, and activated of the JAK2/STAT3 pathway. Furthermore, JAK2/STAT3 pathway inhibitor AG490 can effectively reverse these effects. In conclusion, ticagrelor could play a cardiovascular protective role in diabetic I/R rat, its mechanism may ascribe to the activating JAK2/STAT3 pathway in cardiomyocyte in addition to the PKC pathway. This study provides a basis for the application of ticagrelor in myocardial I/R in the context of diabetes. This article is protected by copyright. All rights reserved.