CAJ | 학술논문

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PI-3K-Akt和ERKI/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.
심기결혈/재관주인기적손상(RMMI)시유다충촉발물、매개물화효응기삼여적복잡생물반응과정,도치염증반응、내피세포손상、혈류장애、심공능이상、심기세포배사화조망.과거이십다년래,진관인문개발료다충심장보호조시(약물성간예)이감소RMMI,단결과병불령인만의.인차,재림상상심구가행화유효적치료조시이감경RMMI유착겁대적개치.아문실험실근래보도료재재관주혹회복공양조기,쾌속반복중단관맥혈류혹양공(결혈혹결양후처리),가감소심기조직혹세포내자유기적생성,감경개초재,감경내피공능적손상,강저점부단백적표체,감소배사화조망.후처리적저사보호작용가능화내원성생성물여선감화일양화담증다、단백매(포괄PI-3K-Akt화ERKI/2)적격활、선립체적ATP의뢰성K+통도개방화선립체통투성전환공관폐유관.여예처리비교,후처리구유동양적보호효응.재장시간재관주후잉유감소경사범위적작용.목전적실험결과화림상관찰증실,재결혈후회복혈공시,후처리적응용재치료결혈/재관주손상방면개계료일개신적치료창구.
Reperfusion of ischemic myocardium 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 unsatisfactory. Therefore, it is extremely valuable to explore some clinically feasible and effective therapeutic strategies that address post-ischemic myocardial injury. Reduction in infarct size and cell death with rapid sequential intermittent interruption of coronary blood flow or oxygen supply at the beginning of reperfusion or reoxygenation ( i. e. ischemic or hypoxic postconditioning) has been recently reported by our laboratory. The protection with postconditioning was expressed as reduction in generation of superoxide radicals, calcium overload, endothelial dysfunction, adhesion molecule expression, necrosis and apoptosis. Mechanisms by postconditioning have been associated with preservation of endogenous autacoids such as adenosine and nitric oxide, activation of protein kinases including PI-3K-Akt and ERK1/2, opening of mitochondrial KATP channels and closing of mitochondrial transition permeability pore. Reduction in infarct size by postconditioning was largely preserved after a prolonged reperfusion and this novel strategy achieved cardioprotection that was comparable to conventional ischemic preconditioning. Experimental studies and clinical observations to date have demonstrated that application of postconditioning at the onset of recovery of blood flow after ischemia opens a new therapeutic strategy in the treatment of ischemia/reperfusion injury.