活性氧的内源性心肌保护作用及其机制

既往认为在心肌缺血/再灌注过程中活性氧是一种有害的细胞损伤因子,但最近研究发现也是可产生细胞保护作用的信号分子.活性氧(reactive oxygen species,ROS)在缺血,再灌注及其内源性心肌保护作用中具有双重作用,内源性心肌保护过程中活性氧主要来自线粒体呼吸链,主要通过mKATP-ROS通路产生;活性氧通过改变细胞氧化还原状态和调节线粒体膜通透性转换孔道开放状态,传递线粒体和细胞之间的信息联系.因此.活性氧不单是缺血/再灌注氧化应激的损伤因子,也是产生内源性心肌保护作用的重要信号分子.     

活性氧的内源性心肌保护作用及其机制

既往认为在心肌缺血/再灌注过程中活性氧是一种有害的细胞损伤因子,但最近研究发现也是可产生细胞保护作用的信号分子.活性氧(reactive oxygen species,ROS)在缺血,再灌注及其内源性心肌保护作用中具有双重作用,内源性心肌保护过程中活性氧主要来自线粒体呼吸链,主要通过mKATP-ROS通路产生;活性氧通过改变细胞氧化还原状态和调节线粒体膜通透性转换孔道开放状态,传递线粒体和细胞之间的信息联系.因此.活性氧不单是缺血/再灌注氧化应激的损伤因子,也是产生内源性心肌保护作用的重要信号分子.     

心肌缺血/再灌注损伤分子信号保护机制的研究进展

缺血/再灌注损伤是一种常见的病理生理改变,近些年来,随着对其机制的大量研究,缺血/再灌注损伤的分子信号保护机制有了许多新的进展.腺苷激动腺苷2A受体(A2AAR),通过Gs蛋白-cAMP信号轴抑制与再灌注相关的炎症反应起保护作用.激活的阿片受体是通过抗细胞凋亡自身激酶信号路径的相互作用来减少再灌注损伤的.缺血后处理的机制也可能涉及到内源性腺苷释放增加.     

活性氧在肝脏缺血再灌注损伤中的研究进展

目的总结活性氧在肝脏缺血再灌注损伤中的发病机理及活性氧防治的最新研究进展。方法通过对CNKI、Pub Med等数据库文献进行检索,就活性氧在肝脏缺血再灌注损伤中的产生、损伤机理以及对近年来在活性氧防治方面的研究进展进行综述。结果在肝脏缺血再灌注损伤中,多形核白细胞、Kupffer细胞、线粒体以及肝组织中的酶产生大量的活性氧。活性氧主要通过破坏细胞膜上寡糖链中的糖分子、体内的不饱和脂肪酸、蛋白质分子、遗传物质、线粒体等导致细胞损伤甚至死亡。目前主要的防治方法为利用酶、维生素、中草药等清除活性氧,减轻肝脏缺血再灌注损伤。结论目前关于活性氧在肝脏缺血再灌注损伤中的研究取得了重要进展,针对活性氧对肝脏造成的损伤也提出了多种可行的防治方法,但要应用于临床还有待进一步深入研究。     

肝移植术后肝缺血再灌注损伤保护作用的研究进展

肝缺血再灌注损伤是肝移植术后最常见的并发症。活性氧生成过多导致的氧化应激、自噬、炎症反应是造成肝缺血再灌注损伤的重要步骤。其中,核转录因子红系2相关因子2被认为是抗氧化反应的主要调节因子,PI3K-Akt-mTOR通路被认为是自噬的重要通路,HMGB1-TLR4-NF-κB通路被认为是导致炎症的关键信号通路,本文将从上述通路及调节分子出发,分别从基因、分子、药物等方面研究对肝缺血再灌注细胞的抗氧化、抗炎、调节自噬作用,探究对肝缺血再灌注细胞的保护作用。     

肝脏缺血后处理的保护作用机制

肝脏缺血后处理是指肝脏在长时间缺血后,在再灌注之前进行一次或数次短暂重复的缺血再灌注,能提高肝脏对长时间缺血的耐受性,减轻缺血再灌注损伤.近几年被证实为一种有效、可控制的新的减轻再灌注损伤的方法.肝脏缺血后处理的保护机制与保护肝窦内皮和肝脏细胞超微结构,减轻活性氧引起的细胞损伤及炎症反应,减轻细胞内及线粒体内钙超载,调控凋亡基因,改变线粒体离子通道开放状态等有关.本文就缺血后处理的机制作一简要综述.     

线粒体呼吸链复合体Ⅲ生成活性氧介导预处理心肌保护作用的研究进展

概述 线粒体呼吸链是心肌缺血/再灌注损伤活性氧(reactive oxygen species,ROS)生成的主要场所.复合体Ⅲ作为线粒体呼吸链的重要组成部分,与其他复合体共同协作,完成电子的传递和氧化磷酸化.最近的一些研究结果表明,复合体Ⅲ在预处理心肌保护中起着重要作用. 目的 通过查阅近年相关的研究文献,对复合体Ⅲ生成ROS介导预处理的心肌保护作用予以综述. 内容 复合体Ⅲ是预处理时生成ROS的主要位点.预处理可通过升高线粒体膜电位(m△Ψ)、改变复合体Ⅲ的活性等机制,介导复合体Ⅲ生成ROS心肌保护信号分子,继而产生心肌保护作用. 趋向 未来的研究会进一步探究预处理时,调控复合体Ⅲ生成ROS信号的具体机制,同时应加强复合体Ⅲ生成ROS介导心肌保护的临床应用,为临床心肌保护提供有力手段.     

缺血后处理减轻心肌缺血损伤的机制与pH假说

缺血后处理是近年来提出的一种减轻缺血/再灌注损伤的新方法,即在全面再灌注前进行反复、短暂的预再灌/停灌干预而达到心肌保护作用,其机制可能与蛋白激酶C和再灌注损伤挽救激酶通路的激活、有害信号转导通路的抑制有关.另有研究显示缺血后处理的心肌保护作用可能与其在缺血心肌再灌注初产生的延迟性酸中毒状态有关.     

七氟烷后处理的心肌保护作用及其机制

背景 大量实验证据表明缺血后处理和药物后处理对心肌再灌注损伤具有确切的保护作用.七氟烷是一种新型的、理想的吸入性麻醉药,被广泛应用于全身麻醉.实验证明七氟烷后处理可以保护心肌对抗缺血/再灌注损伤(ischemia/reperfusion injury,I/RI).目的 通过对近年研究进展的总结对七氟烷后处理的心肌保护作用及机制予以阐述.内容七氟烷后处理可以减少再灌注心肌的梗死面积、线粒体损害和再灌注室性心律失常的发生,改善心脏的血流动力学.七氟烷后处理心肌保护作用复杂且涉及多个方面,如阻断线粒体通透性转运孔(mitochondrial permeability transition pore,mPTP)、激活线粒体ATP敏感性K+通道(mitochondrial KATP-channel,mKATP),激活细胞外信号调节激酶1/2(extracellular signal-regulated kinase 1/2,ERK1/2)以及磷酯酰肌醇-3激酶-丝氨酸/苏氨酸激酶(phosphatidylin ositol-3-kinase-serine/threonine,PI3K-Akt)信号通道等. 趋势 未来的研究除进一步探究七氟烷后处理的心肌保护机制,同时应加强七氟烷后处理的临床应用,为实际工作提供可靠依据.     

线粒体自噬在缺血再灌注损伤中的研究进展

缺血再灌注损伤是指缺血组织或器官再次获得血流灌注时对组织、器官造成的损伤作用.而缺血再灌注损伤时,线粒体即可产生的大量的活性氧且线粒体通透性发生改变从而诱发线粒体白噬.线粒体白噬功能的紊乱与机体多种疾病的发生有着密切的关系.本文旨在介绍近年来线粒体白噬的研究进展,重点阐述其在缺血再灌注损伤中的作用及机制.     

Pharmacological preconditioning with hyperbaric oxygen: can this therapy attenuate myocardial ischemic reperfusion injury and induce myocardial protection via nitric oxide?

Ischemic reperfusion injury (IRI) is an inevitable part cardiac surgery such as coronary artery bypass graft (CABG). While ischemic hypoxia and the ensuing normoxic or hyperoxic reperfusion are critical to the initiation and propagation of IRI, conditioning myocardial cells to an oxidative stress prior to IRI may limit the consequences of this injury. Hyperbaric oxygen (HBO2) is a modality of treatment that is known to generate an oxidative stress. Studies have shown that treatment with HBO2 postischemia and reperfusion is useful in ameliorating myocardial IRI. Moreover, preconditioning the myocardium with HBO2 before reperfusion has demonstrated a myocardial protective effect by limiting the infarct size post ischemia and reperfusion. Current evidence suggests that HBO2 preconditioning may partly attenuate IRI by stimulating the endogenous production of nitric oxide (NO). As NO has the capacity to reduce neutrophil sequestration, adhesion and associated injury, and improve vascular flow, HBO2 preconditioning induced NO may play a role in providing myocardial protection during interventions that involve an inevitable episode of IRI. This current opinion review article attempts to suggest that HBO2 may be used to pharmacologically precondition and protect the myocardium from the effects of IRI that is known to occur during cardiac surgery.     

Reactive Oxygen Species Play a Biphasic Role in Brain Ischemia

Objective: Reactive oxygen species (ROS) are the essential mechanism involving in the ischemic process. Due to their complex characteristics, the precise effects of ROS on post-ischemic neurons remain uncertain. This study aimed to investigate the potential role of ROS in brain ischemia. Methods: Dynamic ROS levels in the perifocal cortex were evaluated after right middle cerebral artery occlusion (MCAO) of SD rats. Furthermore the role of ROS was assessed following delayed treatment with the ROS scavenger dimethylthiourea (DMTU) after brain ischemia. Results: ROS levels markedly increased at 1 hr after reperfusion and then gradually decreased as the post-reperfusion time interval increased. ROS levels reached their lowest point at 3 days after reperfusion before increasing and showing a second peak at 7 days after reperfusion. ROS levels negatively correlated with neurological function scores. Delayed DMTU treatment after stroke worsened neurological outcomes, decreased microvessel density and inhibited stress-activated protein kinase activation. Conclusion: ROS may play a biphasic role in cerebral ischemia. Namely, ROS may induce damage during the injury phase of brain ischemia and participate in improving neurological function during the recovery phase.     

Reduction of myocardial ischemic injury with oxygen-derived free radical scavengers

Experimental data suggesting that oxygen-derived free radicals may play a role in the myocardial injury associated with ischemia and reperfusion are presented. In several studies of prolonged global myocardial ischemia, the administration of free radical scavenging agents, such as superoxide dismutase, catalase, and mannitol, resulted in significantly better recovery of left ventricular function following reperfusion. In a region-at-risk model of localized myocardial ischemia, both superoxide dismutase and allopurinol significantly reduced the extent of myocardial necrosis that developed following reversible coronary arterial branch occlusion. The manner in which oxygen-derived free radicals may be harmful is examined. In particular, the possibility that these toxic species are involved in the exacerbation of the ischemic injury that develops upon reflow and reoxygenation is examined.     

Myocardial ischaemia and reperfusion injury: reactive oxygen species and the role of neutrophil

A growing body of evidence suggests that oxygen radicals can mediate myocardial tissue injury during ischaemia and, in particular, during reperfusion. This review focuses on the role of neutrophil as a mediator of myocardial damage. Upon reperfusion, neutrophils accumulate and produce an inflammatory response in the myocardium that is responsible, in part, for the extension of tissue injury associated with reperfusion. It has shown that the inhibition of neutrophil accumulation and adhesion is associated with decreased infarct size. This strongly suggests that myocardial cells at risk region undergo irreversible changes upon reperfusion and accumulation of neutrophils. Several pharmacological agents (ibuprofen, allopurinol, prostacyclin, and prostaglandin E analogues) protect the myocardium from reperfusion injury. In addition, the mechanisms by which these agents act and directions of research that may lead to therapeutically useful approaches are also discussed in this review.     

七氟醚缺血后处理对心脏瓣膜置换术中血清肌钙蛋白T和心肌细胞内活性氧簇的影响

目的观察七氟醚缺血后处理对风湿性心脏病(RHD)患者单瓣膜置换术中血清心肌肌钙蛋白T(cTnT)和心肌细胞内活性氧簇(ROS)的影响,探讨其对缺血-再灌注心肌的保护作用。方法择期行心脏单瓣膜置换术的RHD患者24例,随机均分为两组,七氟醚缺血后处理组(S组)行1MAC七氟醚缺血后处理5min,对照组(C组)不予七氟醚缺血后处理。采集动脉血检测cTnT,采用二氯荧光素法测定心肌细胞内ROS水平。结果与术前比较,主动脉开放后1～4h时两组血清cTnT浓度均明显升高(P<0.05),但S组明显低于C组(P<0.05)。与主动脉阻断前比较,主动脉开放后1h两组心肌细胞内ROS水平均显著增加(P<0.05),但S组明显低于C组(P<0.05)。结论七氟醚缺血后处理心肌保护作用可能与抑制缺血-再灌注心肌细胞内ROS过度生成有关。     

Reactive oxygen species as mediators of cardiac injury and protection: the relevance to anesthesia practice

Reactive oxygen species (ROS) are central to cardiac ischemic and reperfusion injury. They contribute to myocardial stunning, infarction and apoptosis, and possibly to the genesis of arrhythmias. Multiple laboratory studies and clinical trials have evaluated the use of scavengers of ROS to protect the heart from the effects of ischemia and reperfusion. Generally, studies in animal models have shown such effects. Clinical trials have also shown protective effects of scavengers, but whether this protection confers meaningful clinical benefits is uncertain. Several IV anesthetic drugs act as ROS scavengers. In contrast, volatile anesthetics have recently been demonstrated to generate ROS in the heart, most likely because of inhibitory effects on cardiac mitochondria. ROS are involved in the signaling cascade for cardioprotection induced by brief exposure to a volatile anesthetic (termed "anesthetic preconditioning"). ROS, therefore, although injurious in large quantities, can have a paradoxical protective effect within the heart. In this review we provide background information on ROS formation and elimination relevant to anesthetic and adjuvant drugs with particular reference to the heart. The sources of ROS, the means by which they induce cardiac injury or activate protective signaling pathways, the results of clinical studies evaluating ROS scavengers, and the effects of anesthetic drugs on ROS are each discussed.     

P-选凝素与心肌缺血-再灌注损伤

研究心肌缺血 -再灌注损伤中 P-选凝素 ( P- selectin)的重要作用。P- selectin是一种糖蛋白黏附因子 ,存在于内皮细胞和血小板 ,并介导血小板、内皮细胞和多形核白细胞 ( PMNs)等之间的相互作用 ,且与一氧化氮有着密切的关系 ,形成了许多复杂的炎症病理过程 ,在心肌缺血 -再灌注损伤中起到了关键的作用。特别是 P- selectin与晚期再灌注损伤、血小板及心肌损伤中治疗作用、最新的 P- selectin基因缺陷小鼠和糖尿病小鼠等的心肌缺血 -再灌注损伤中表现的深入研究 ,使其在缺血 -再灌注损伤中的重要性和复杂性显得更加突出。     

Coronary trapping of a complement activation product (C3a des-Arg) during myocardial reperfusion in open-heart surgery

Accumulation of complement factors has been found to occur in the myocardium after infarction. We studied the possibility that the complement activation product C3a des-Arg is trapped within the coronary circulation during reperfusion of the ischemic myocardium. In 11 patients undergoing routine coronary artery bypass grafting, arterial blood was sampled before, during and after cardiopulmonary bypass. Blood was drawn from the coronary sinus concomitantly with arterial blood sampling 5 and 30 min after release of the aortic cross-clamp (n = 10). From a preoperative value of 92 +/- 13 ng/ml, C3a des-Arg rose during CPB to a maximum of 1816 +/- 393 at the end of CPB. Following reperfusion for 5 min, C3a des-Arg was 1284 +/- 232 ng/ml in arterial and 1106 +/- 100 in coronary sinus blood, a significant difference (p less than 0.05). The amount of C3a des-Arg trapped in the heart at 5-min reperfusion showed positive correlation with its arterial concentration (p less than 0.05). No significant difference was found after 30 min of reperfusion. Complement activation products trapped in the heart in the early reperfusion period may play a pathogenetic role in myocardial ischemia-reperfusion injury.