Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion
Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion
复制标题
抑制血管过氧化物酶可减轻缺血再灌注引起的心功能障碍和细胞凋亡
DOI：
10.1139/y2012-066
复制
发表时间：
2012-07-01
影响因子：
2.1
通讯作者：
Peng, Jun
中科院分区：
文献类型：
--
作者：
Li, Ting-Ting;Zhang, Yi-Shuai;Peng, Jun
髓过氧化物酶（MPO）参与心肌缺血再灌注（IR）损伤，血管过氧化物酶（VPO）是新近发现的MPO同工酶。本研究旨在探讨VPO是否参与IR诱导的心功能不全和细胞凋亡。在Langendorff大鼠心肌缺血再灌注模型上，测定心功能参数（左室压力、左室压力与冠脉流量的最大导数）、肌酸激酶（CK）活性、细胞凋亡、VPO 1活性。在细胞（大鼠心脏衍生的H9 c2细胞）缺氧-复氧（HR）模型中，检测细胞凋亡、VPO活性和VPO 1 mRNA表达。在离体心脏中，IR引起心功能显著下降，细胞凋亡、CK和VPO活性显著增加。这些影响被减弱的药理学抑制VPO。在体外，药物抑制VPO活性或沉默VPO 1表达显着抑制HR诱导的细胞凋亡。结果提示，VPO活性增高是IR所致心功能不全的重要原因，抑制VPO活性对IR损伤心肌具有潜在的临床保护价值。
Myeloperoxidase (MPO) is involved in myocardial ischemia-reperfusion (IR) injury and vascular peroxidase (VPO) is a newly identified isoform of MPO. This study was conducted to explore whether VPO is involved in IR-induced cardiac dysfunction and apoptosis. In a rat Langendorff model of myocardial IR, the cardiac function parameters (left ventricular pressure and the maximum derivatives of left ventricular pressure and coronary flow), creatine kinase (CK) activity, apoptosis, VPO1 activity were measured. In a cell (rat-heart-derived H9c2 cells) model of hypoxia-reoxygenation (HR), apoptosis, VPO activity, and VPO1 mRNA expression were examined. In isolated heart, IR caused a marked decrease in cardiac function and a significant increase in apoptosis, CK, and VPO activity. These effects were attenuated by pharmacologic inhibition of VPO. In vitro, pharmacologic inhibition of VPO activity or silencing of VPO1 expression significantly suppressed HR-induced cellular apoptosis. Our results suggest that increased VPO activity contributes to IR-induced cardiac dysfunction and inhibition of VPO activity may have the potential clinical value in protecting the myocardium against IR injury.