title: GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats.
abstract: Hydrogen sulfide (H2S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to determine the protective effect of slow-releasing H2S donor GYY4137 on myocardial ischemia and reperfusion (I/R) injury and to investigate the possible signaling mechanisms involved. Male Sprague-Dawley rats were treated with GYY4137 at 12.5 mg/(kg·day), 25 mg/(kg·day) or 50 mg/(kg·day) intraperitoneally for 7 days. Then, rats were subjected to 30 minutes of left anterior descending coronary artery occlusion followed by reperfusion for 24 hours. We found that GYY4137 increased the cardiac ejection fraction and fractional shortening, reduced the ischemia area, alleviated histological injury and decreased plasma creatine kinase after myocardial I/R. Both H2S concentration in plasma and cystathionine-γ-lyase (CSE) activity in the myocardium were enhanced in the GYY4137 treated groups. GYY4137 also decreased malondialdehyde and myeloperoxidase levels in serum, attenuated superoxide anion level and suppressed phosphorylation of mitogen activated protein kinases in the myocardium after I/R. Meanwhile, GYY4137 increased the expression of Bcl-2 but decreased the expression of Bax, caspase-3 activity and apoptosis in the myocardium. The data suggest that GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis.
authors.affiliation: The Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Meng
authors.affiliation: The Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: The Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Bai
authors.affiliation: The Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Xie
authors.affiliation: The Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Liyang
authors.initials: L
authors.lastname: Shan
authors.affiliation: Neurobiology Group, Life Sciences Institute and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Moore
authors.affiliation: The Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
keywords: apoptosis; hydrogen sulfide; ischemia and reperfusion; myocardial infarction; oxidative stress