|Oxid Med Cell Longev. 2017;2017:2186383. doi: 10.1155/2017/2186383. Epub 2017 Jul 26.|
Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment-Induced Cardioprotection against Ischemia-Reperfusion Injury in Rats.
Sun HJ1, Lu Y2, Wang HW1, Zhang H3, Wang SR4, Xu WY1, Fu HL1, Yao XY5, Yang F6, Yuan HB1.
Department of Anesthesiology, Changzheng Hospital Affiliated to Second Military Medical University, No. 415 Fengyang Road, Shanghai 200003, China.
Department of Neurology, PLA Rocket Force General Hospital, No. 16 Xinjiekouwai Street, Beijing 100088, China.
Department of Anesthesiology, PLA Rocket Force General Hospital, No. 16 Xinjiekouwai Street, Beijing 100088, China.
Nursing School of Shanghai Jiguang Polytechnic College, No. 2859 Shuichan Road, Shanghai 201901, China.
Hebei North University School of Medicine, Zhangjiakou, Hebei 075000, China.
School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, China.
Propofol pretreatment before reperfusion, or propofol conditioning, has been shown to be cardioprotective, while its mechanism is unclear. The current study investigated the roles of endocannabinoid signaling in propofol cardioprotection in an in vivo model of myocardial ischemia/reperfusion (I/R) injury and in in vitro primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. The results showed that propofol conditioning increased both serum and cell culture media concentrations of endocannabinoids including anandamide (AEA) and 2-arachidonoylglycerol (2-AG) detected by LC-MS/MS. The reductions of myocardial infarct size in vivo and cardiomyocyte apoptosis and death in vitro were accompanied with attenuations of oxidative injuries manifested as decreased reactive oxygen species (ROS), malonaldehyde (MDA), and MPO (myeloperoxidase) and increased superoxide dismutase (SOD) production. These effects were mimicked by either URB597, a selective endocannabinoids degradation inhibitor, or VDM11, a selective endocannabinoids reuptake inhibitor. In vivo study further validated that the cardioprotective and antioxidative effects of propofol were reversed by selective CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251. We concluded that enhancing endogenous endocannabinoid release and subsequent activation of CB2 receptor signaling represent a major mechanism whereby propofol conditioning confers antioxidative and cardioprotective effects against myocardial I/R injury.