Objective: It remains unknown whether insulin-like growth factor-1 (IGF-1) can attenuate myocardial ischemia/reperfusion (I/R) injury in vivo by activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. This study investigated the possible interaction of IGF-1 with the PI3K/Akt pathway in cardioprotection against in vivo myocardial I/R injury in rats.
Methods: We established a myocardial I/R model in rats through left anterior descending artery ligation for 40 minutes followed by 6 hours reperfusion. The PI3K/Akt inhibitor, LY294002 (0.3 mg/kg), was injected through the caudal vein 30 minutes before myocardial ischemia, and IGF-1 (1 µg/kg or 5 µg/kg) was injected through the caudal vein 10 minutes before myocardial ischemia.
Results: IGF-1 treatment decreased myocardial infarct size; myocardial cell apoptosis; and serum lactate dehydrogenase, creatine kinase MB, and cardiac troponin I levels in rats with myocardial I/R in vivo. Moreover, IGF-1 treatment led to significant increases in expression levels of p-Akt (Ser473) and B cell lymphoma 2, while reducing expression levels of caspase-9 mRNA and cleaved caspase-9 protein in rats with myocardial I/R. However, pretreatment with LY294002 significantly reduced the cardioprotective effects of IGF-1.
Conclusion: Treatment with IGF-1 may confer cardiac protection against in vivo myocardial I/R injury via the PI3K/Akt pathway in rats.
Keywords: Bcl-2; IGF-1; PI3K/Akt pathway; apoptosis; cardioprotection; caspase 9; creatine kinase; lactate dehydrogenase; myocardial I/R injury; troponin I.