Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment-Induced Cardioprotection against Ischemia-Reperfusion Injury in Rats.
Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment-Induced Cardioprotection against Ischemia-Reperfusion Injury in Rats.
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内源性大麻素受体 2 的激活作为异丙酚预处理诱导的大鼠缺血再灌注损伤心脏保护机制
DOI：
10.1155/2017/2186383
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发表时间：
2017
影响因子：
--
通讯作者：
Yuan HB
中科院分区：
文献类型：
--
作者：
Sun HJ;Lu Y;Wang HW;Zhang H;Wang SR;Xu WY;Fu HL;Yao XY;Yang F;Yuan HB
再灌注前丙泊酚预处理或丙泊酚预处理已被证明具有心脏保护作用，但其机制尚不清楚。本研究探讨了内源性大麻素信号转导在丙泊酚心肌保护中的作用，在体内模型的心肌缺血/再灌注（I/R）损伤和体外原代心肌细胞缺氧/复氧（H/R）损伤。结果表明，异丙酚预处理增加了内源性大麻素包括花生四烯酸酰胺（AEA）和2-花生四烯酸甘油（2-AG）的血清和细胞培养液浓度。在体内心肌梗死范围和体外心肌细胞凋亡和死亡的减少伴随着氧化损伤的减轻，表现为活性氧（ROS），丙二醛（MDA），和髓过氧化物酶（MPO），并增加超氧化物歧化酶（SOD）的产生。这些作用被URB 597（一种选择性内源性大麻素降解抑制剂）或VDM 11（一种选择性内源性大麻素再摄取抑制剂）模仿。在体研究进一步证实，选择性CB 2受体拮抗剂AM 630可逆转丙泊酚的心肌保护和抗氧化作用，而CB 1受体拮抗剂AM 251则不能逆转丙泊酚的心肌保护和抗氧化作用。我们的结论是，增强内源性内源性大麻素的释放和随后的激活CB 2受体信号传导的主要机制，丙泊酚空调赋予抗氧化和心脏保护作用，对心肌I/R损伤。
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.
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作者：
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DOI：
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