Cardiac ischemia-reperfusion (I/R) injury remains a challenge for clinicians, which initiates with energy metabolism disorder. The present study was designed to investigate the protective effect of Notoginsenoside R1 (NR1) on I/R-induced cardiac injury and underlying mechanism. Male Sprague-Dawley rats were subjected to 30 min occlusion of left coronary anterior descending artery followed by reperfusion with or without NR1 pretreatment (5 mg/kg/hour). In vitro, H9c2 cells were cultured in oxygen and glucose deprivation/reoxygenation (OGD/R) condition after NR1 (0.1 mM), Rho kinase (ROCK) inhibitor Y-27632 (10 μM) or RhoA/ROCK activator U-46619 (10 nM) administration. Myocardial infarct size, myocardial histology and cardiac function were evaluated. Myoﬁbril and mitochondria morphology were observed by transmission electron microscopy. F-actin and apoptosis were determined by immunoﬂuorescence and TUNEL staining. ATP and AMP content were assessed by ELISA. P-AMPK, ATP synthase subunits, apoptosis-related molecules and the level and activity of ROCK were determined by Western blotting. We found NR1 pretreatment ameliorated myocardial infarction, histological injury and cardiac function induced by I/R. Furthermore, similar to the effect of Y-27632, NR1 improved H9c2 cell viability, maintained actin skeleton and mitochondria morphology, and apoptosis induced by OGD/R. Importantly, NR1 prevented energy abnormity, inhibited the expression and activation of ROCK, restored the expression of ATP5D both in vivo and in vitro. Whereas, U-46619 suppressed the effect of NR1. These results prove NR1 as an agent able to prevent I/R-induced energy metabolism disorder via inhibiting ROCK and enhancing ATP5D, which at least partially contributes to its protection against cardiac I/R injury.
- Notoginsenoside R1
- myocardium I/R injury
- ROCK inhibition
- energy deficit
- Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology