Mitochondria-targeted hydrogen sulfide donor AP39 improves neurological outcomes after cardiac arrest in mice.
Mitochondria-targeted hydrogen sulfide donor AP39 improves neurological outcomes after cardiac arrest in mice.
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DOI：
10.1016/j.niox.2015.05.001
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Ichinose F
中科院分区：
文献类型：
--
作者：
Ikeda K;Marutani E;Hirai S;Wood ME;Whiteman M;Ichinose F
线粒体靶向硫化氢供体AP 39 [（10-氧代-10-（4-（3-硫代-3H-1，2-二巯基-5基）苯氧基）癸基）三苯基溴化鏻]在体外对氧化应激表现出细胞保护作用。我们研究了AP 39是否改善了心脏骤停（CA）和心肺复苏（CPR）小鼠的神经功能和长期存活率。使成年C57 BL/6雄性小鼠经受8分钟的CA和随后的CPR。我们检查了在CPR前2分钟静脉注射AP 39（10、100、1000 nmol kg-1）或溶剂的效果（实验1）。评估了全身氧化应激水平、线粒体通透性转换和组织学脑损伤。我们还检查了在自主循环恢复（ROSC）后1分钟静脉内给予AP 39（10，1000 nmol kg-1）或溶媒的作用（实验2）。ROSC定义为恢复窦性心律，平均动脉压> 40 mm Hg，持续至少10秒。接受CA/CPR的溶媒处理小鼠的神经功能和10天存活率较差（实验1; 15%，实验2; 23%）。在CPR前2分钟给予AP 39（100和1000 nmol kg−1）显著改善了CA/CPR后的神经功能和10天生存率（分别为54%和62%）。CPR前给予AP 39可减弱CA/CPR后线粒体通透性转换孔开放、活性氧产生和神经元变性。在ROSC后1分钟给予10 nmol kg−1的AP 39，而不是1000 nmol kg−1，显著改善了CA/CPR后的神经功能和10天存活率（69%）。目前的结果表明，在CPR时或在ROSC后施用靶向的硫化物供体AP 39通过维持线粒体完整性和降低氧化应激改善了CA/CPR后的神经功能和长期存活率。
Mitochondria-targeted hydrogen sulfide donor AP39, [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5yl)phenoxy)decyl) triphenylphosphonium bromide], exhibits cytoprotective effects against oxidative stress in vitro. We examined whether or not AP39 improves neurological function and long term survival in mice subjected to cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Adult C57BL/6 male mice were subjected to 8 min of CA and subsequent CPR. We examined the effects of AP39 (10, 100, 1000 nmol kg−1) or vehicle administered intravenously at 2 min before CPR (Experiment 1). Systemic oxidative stress levels, mitochondrial permeability transition, and histological brain injury were assessed. We also examined the effects of AP39 (10, 1000 nmol kg−1) or vehicle administered intravenously at 1 min after return of spontaneous circulation (ROSC) (Experiment 2). ROSC was defined as the return of sinus rhythm with a mean arterial pressure > 40 mm Hg lasting at least 10 seconds. Vehicle treated mice subjected to CA/CPR had poor neurological function and 10-day survival rate (Experiment 1; 15%, Experiment 2; 23%). Administration of AP39 (100 and 1000 nmol kg−1) 2 min before CPR significantly improved neurological function and 10-day survival rate (54% and 62%, respectively) after CA/CPR. Administration of AP39 before CPR attenuated mitochondrial permeability transition pore opening, reactive oxygen species generation, and neuronal degeneration after CA/CPR. Administration of AP39 1 min after ROSC at 10 nmol kg−1, but not at 1000 nmol kg−1, significantly improved neurological function and 10 day-survival rate (69%) after CA/CPR. The current results suggest that administration of mitochondria-targeted sulfide donor AP39 at the time of CPR or after ROSC improves neurological function and long term survival rates after CA/CPR by maintaining mitochondrial integrity and reducing oxidative stress.
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影响因子：
8.8
作者：
Han F;Da T;Riobo NA;Becker LB
通讯作者：
Becker LB
影响因子：
--
作者：
Le Trionnaire, Sophie;Perry, Alexis;Whiteman, Matthew
通讯作者：
Whiteman, Matthew
DOI：
10.1073/pnas.0705891104
发表时间：
2007-09-25
影响因子：
11.1
作者：
Elrod, John W.;Calvert, John W.;Lefer, David J.
通讯作者：
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影响因子：
2.9
作者：
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通讯作者：
Hopkins, KJ
影响因子：
6.5
作者：
Pusswald, G;Fertl, E;Auff, E
通讯作者：
Auff, E