摘要
心肌缺血/再灌注引起的损伤(RMMI)是由多种触发物、媒介物和效应器参与的复杂生物反应过程,导致炎症反应、内皮细胞损伤、血流障碍、心功能异常、心肌细胞坏死和凋亡。过去二十多年来,尽管人们开发了多种心脏保护措施(药物性干预)以减少RMMI,但结果并不令人满意。因此,在临床上寻求可行和有效的治疗措施以减轻RMMI有着极大的价值。我们实验室近来报道了在再灌注或恢复供氧早期,快速反复中断冠脉血流或氧供(缺血或缺氧后处理),可减少心肌组织或细胞内自由基的生成,减轻钙超载,减轻内皮功能的损伤,降低黏附蛋白的表达,减少坏死和凋亡。后处理的这些保护作用可能和内源性生成物如腺苷和一氧化氮增多、蛋白酶(包括PI3KAkt和ERK1/2)的激活、线粒体的ATP依赖性K+通道开放和线粒体通透性转换孔关闭有关。与预处理比较,后处理具有同样的保护效应。在长时间再灌注后仍有减少梗死范围的作用。目前的实验结果和临床观察证实,在缺血后恢复血供时,后处理的应用在治疗缺血/再灌注损伤方面开启了一个新的治疗窗口。
Reperfusion of ischemic myneardium is a complex biological process that involves multiple triggers, mediators and end-effectors, resulting in inflammatory and endothelial damage blood flow defects, cardiac dysfunction, necrosis and apoptosis. In the last two decades, although considerable effort has been exerted in exploring cardioprotective strategies in an attempt to limit reperfusion-induced myocardial injury, most of the clinical trails using various pharmacological agents to attenuate reperfusion injury have been rather unsatisfac, tory. Therefore, it is extremely valuable to explore some clinically feasible and effective therapeutic strategies that address post-isehemic myocardial injury. Reduction in inthret size and cell dealh with rapid sequential intermittent interruption of coronary blood flow or oxygen supply at the beginning of repeffusinn or reoxygenation （ i, e. ischemie or hypnxic postconditinning） has been recently reported by our laboratory. The protection with postconditioning was expressed as reduction in gene,＇ation of superoxide radicals, calcium overload, endothelial dysfunction, adhesioll molecule expression, neernsis and apoptosis. Mechanisms by poslconditioning have been associated with preservation of endogenous autacoids such as adenosine and nitric oxide, aetivation of protein kinases including PI-3K-Akt and ERK1/2, opening of milochondrial KATP, channels and elosing of mitochondrial transition permeability pore. Reduction in infarct size by postconditioning was largely preserved after a prolonged reperfusion and this novel strategy achieved eardioprotection that was comparable to conventional ischemie preconditioning. Experimental studies and clinical observations to dale have demnnstrated that application of postennditioning at the onset of reeovery of blood tlow after ischemia opens a new therapeutic strategy in the treatment of ischemia/reperfusion injury.
出处
《心脏杂志》
CAS
2006年第1期1-7,13,共8页
Chinese Heart Journal
基金
grantfromtheNationalInstituteofHealth(HL64886)andfundsfromtheCarlyleFraserHeartCenterofEmoryUniversitySchoolofMedicine.
关键词
后处理
预处理
缺血/再灌注
损伤
心脏
posteonditioning
preconditioning
isehemia/repefusion injury
heart
