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Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest

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收录情况： ◇ SCIE

作者：
Hai, Kerong[1,2] ; Chen, Guo[3] ; Gou, Xueyan[4] ; Jang, Haixia[5] ; Gong, Deying[1] ; Cheng, Yan[1] ; Gong, Chansheng[1,3] ; Li, Xinghuan[1,3] ; Liu, Yuqi[1,3] ; Li, Huan[1] ; Zhang, Gang[3] ; Yang, Linghui[1] ; Ke, Bowen[1] ; Liu, Jin[1,3] ;
机构： [1]Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]The First Clinical Medical College of Northwest University for Nationalities, The People’s Hospital of Ningxia Hui Nationality Autonomous Region, Yinchuan, Ningxia, China. [3]Department of Anesthesiology, West China Hospital Sichuan University, Chengdu, Sichuan, China. [4]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China. [5]Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
出处：
DOI： 10.1097/CCM.0000000000003552
ISSN：

关键词： cardiac arrest cardiopulmonary resuscitation monoacylglycerol lipase myocardial function postresuscitation

摘要：
Objectives: Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. Design: Prospective randomized laboratory study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rat (n = 96). Interventions: Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. Measurements and Main Results: Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. Conclusions: Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.

基金：
National Scientific Foundation of ChinaNational Natural Science Foundation of China [81571353, 81701873]; Key Research Project of Science and Technology Department of Sichuan Province [2018SZ0155]; Central University Basic Scientific Research Expenses [31920140073]; 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZY2016101, ZY2016203]
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外文
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中科院(CAS)分区：
出版当年[2020]版：
大类 | 1 区 医学
小类 | 2 区 危重病医学
最新[2023]版：
大类 | 1 区 医学
小类 | 2 区 危重病医学
JCR分区：
出版当年[2019]版：
Q1 CRITICAL CARE MEDICINE
最新[2023]版：
Q1 CRITICAL CARE MEDICINE

影响因子： 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

第一作者：
第一作者机构： [1]Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]The First Clinical Medical College of Northwest University for Nationalities, The People’s Hospital of Ningxia Hui Nationality Autonomous Region, Yinchuan, Ningxia, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Hai Kerong,Chen Guo,Gou Xueyan,et al.Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest[J].CRITICAL CARE MEDICINE.2019,47(2):E144-E151.doi:10.1097/CCM.0000000000003552.
APA：
Hai, Kerong,Chen, Guo,Gou, Xueyan,Jang, Haixia,Gong, Deying...&Liu, Jin.(2019).Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest.CRITICAL CARE MEDICINE,47,(2)
MLA：
Hai, Kerong,et al."Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest".CRITICAL CARE MEDICINE 47..2(2019):E144-E151

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