Hydrogen-rich saline alleviates inflammation and apoptosis in myocardial I/R injury via PINK-mediated autophagy

Abstract:

Ischemia/reperfusion (I/R)‑induced inflammatory reaction is one of the most important elements in myocardial I/R injury. In addition, autophagy serves an important role in normal cardiac homeostasis, and obstructions to the autophagy process lead to severe consequences for the heart. Hydrogen exerts an effective therapeutic role in numerous diseases associated with I/R injury via its anti‑inflammation, anti‑apoptosis and anti‑oxidative properties. Therefore, the present study investigated the effect of hydrogen on the myocardial inflammation response and apoptosis in myocardial ischemic/reperfusion (MI/R) injury, and further explored the mechanism of PTEN‑induced kinase 1 (PINK1)/Parkin‑induced mitophagy in the protection of hydrogen on MI/R injury. MI/R injury was performed by surgical ligation of the left coronary artery in vivo and H9C2 cell injury was performed by hypoxia/reoxygenation (H/R) in vitro. Hydrogen‑rich saline was administered twice through intraperitoneal injection at a daily dose of 10 ml/kg following the operation in the in vivo model, and hydrogen‑rich medium culture was used for cells instead of normal medium in vitro. The infarction size of hearts, the levels of creatinine kinase‑muscle/brain (CK‑MB) and cardiac troponin I (cTnI), cardiac function, cell viability and lactate dehydrogenase (LDH) release, levels of cytokines, apoptosis and the expression of autophagy‑associated proteins were detected in the different treatment groups in vivo and in vitro. The results demonstrated that treatment with hydrogen improved the myocardial infarction size of hearts, cardiac function, apoptosis and cytokine release following MI/R in rats. In vitro, hydrogen improved cell viability and LDH release following hypoxia/reoxygenation in myocardial cells. In addition, it was demonstrated that hydrogen exerted an anti‑inflammatory and anti‑apoptotic effect in myocardial cells induced by H/R via PINK1/Parkin mediated autophagy. These results suggested that hydrogen‑rich saline alleviated the inflammation response and apoptosis induced by MI/R or H/R in vivo or in vitro, and that hydrogen‑rich saline contributed to the increased expression of proteins associated with autophagy. In summary, the present study indicated that treatment with hydrogen‑rich saline improved the inflammatory response and apoptosis in MI/R via PINK1/Parkin‑mediated mitophagy.