Treatment with D-beta-hydroxybutyrate protects heart from ischemia/reperfusion injury in mice

摘要

The present study was designed to examine the protection of D-5-hydroxybutyrate (BHB) against ischemia/ reperfusion (I/R) injury in heart and investigate its underlying mechanism. Male adult mice were exposed to 30 min of ischemia and 24 h of reperfusion. Osmotic pumps were implanted subcutaneously 5 min before reperfusion for continuous delivery of the exogenous BHB (1.6 mmol/kg/24 h). Treatment with BHB reduced infarct size and levels of cardiac troponin I, creatine kinase and lactate dehydrogenase in serum, attenuated apoptosis in myocardium, and preserved cardiac function of I/R mice. Importantly, treatment of I/R mice with BHB promoted autophagic flux, evidenced by reduced the ratio of LC3-II/LC3-I and protein expression of p62 and enhanced protein expression of lysosome associated membrane protein-2 (Lamp2) in myocardium. Treatment of I/R mice with BHB reduced mitochondrial formation of reactive oxygen species, enhanced adenosine triphosphate production, attenuated mitochondrial swelling, and partly restored mitochondrial membrane potential in myocardium. Furthermore, treatment of I/R mice with BHB abated oxidative stress and attenuated endoplasmic reticulum stress in myocardium. Our results indicated that treatment with exogenous BHB protected heart from I/R injury in mice.