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.     

吸人麻醉药后处理心肌保护作用机制的研究进展

背景 吸入麻醉药后处理（inhalational anesthetics postconditioning,APO）是指在缺血后再灌注早期给予一定浓度吸入麻醉药处理。APO具有心肌保护作用,其作用机制目前尚未完全阐明。目的 对APO心肌保护作用机制的研究进展进行回顾和总结。内容 APO的心肌保护的信号转导机制与缺血后处理有很多相似之处,可能是通过刺激心肌产生触发物,活化相关信号通路,激活效应因子,发挥后处理效应。目前研究已证实APO心肌保护作用与激活再灌注损伤补救激酶（reperfusion injury salvage kinase,RISK）,抑制再灌注心肌细胞凋亡及线粒体等有关。趋向 APO心肌保护作用机制错综复杂,弄清这些复杂的信号转导机制对于揭示APO效应的原理,促进临床推广具有重要的指导意义。     

缺血后处理心肌保护作用的研究进展

缺血后处理（一个长时间缺血后,在再灌注开始时,通过反复短暂间断的缺血／再灌注而诱导的心肌保护现象）是最近提出的一种和缺血预处理一样有心肌保护作用的新的治疗措施,被认为是减少缺血／再灌注损伤的“末戏”。因为能够在缺血后再灌注时实施,可用于突发的不可预知的心肌缺血事件,有极大的基础研究意义和临床应用前景。现就其在心肌保护方面的研究作一简要综述。     

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.     

心肌保护新策略--缺血后处理

缺血后处理(ischemic postconditioning)是近年来提出的一种新的心肌保护方法,即再灌注后对缺血心肌反复进行再缺血处理,以减轻缺血再灌注损伤.其机制可能与抑制氧自由基堆积、中性粒细胞黏附、心肌细胞凋亡和细胞内钙超载有关.由于缺血后处理可在不可预见的心肌缺血后进行,且操作方便,因此在临床上可能具有较大的应用价值.     

心肌保护新策略——缺血后处理

缺血后处理（ischernjc postconditioning）是近年来提出的一种新的心肌保护方法，即再灌注后对缺血心肌反复进行再缺血处理，以减轻缺血再灌注损伤。其机制可能与抑制氧自由基堆积、中性粒细胞黏附、心肌细胞凋亡和细胞内钙超载有关。由于缺血后处理可在不可预见的心肌缺血后进行，且操作方便，因此在临床上可能具有较大的应用价值。     

吸入麻醉药后处理心肌保护作用机制的研究进展

背景 吸入麻醉药后处理(inhalational anesthetics postconditioning,APO)是指在缺血后冉灌注早期给予一定浓度吸入麻醉药处理.APO具有心肌保护作用,其作用机制目前尚未完全阐明.目的 对APO心肌保护作用机制的研究进展进行回顾和总结.内容 APO的心肌保护的信号转导机制与缺血后处...     

δ受体在芬太尼后处理和肢体远隔缺血后处理对大鼠心肌缺血/再灌注损伤保护效应中作用的实验研究

目的 探讨δ受体在芬太尼后处理和肢体远隔缺血后处理对大鼠心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)保护作用机制中的地位.方法 通过结扎冠状动脉左前降支(left anterior descending coronary artery,LAD)造成局部心肌缺血30 min后开放血流再灌注180 min建立心肌I/RI模型.将72只大鼠按随机数字表法随机平均分为4组(每组18只),分别在结扎LAD 15 min时给予芬太尼(30 μg/kg)、远隔缺血后处理、联合应用芬太尼和远隔缺血后处理或生理盐水(对照).在结扎LAD前5 min,将每组大鼠平均分成A和B两个亚组,分别静脉注入生理盐水和δ受体拮抗剂Nahrindole hydrochloride (NTD).再灌注180 min时,测定血浆肌酸激酶MB同工酶(creatine kinase isoenzyme MB,CK-MB)和血清心肌肌钙蛋白I(cardiac troponin I,cTnI)活性,采用伊文氏蓝和氯化三苯基四氮唑染色法测定心肌梗死面积(infarct size,IS％)值.结果 C-A亚组、F-A亚组、R-A亚组、F-R-A亚组、C-B亚组、F-B亚组、R-B亚组和F-R-B亚组的IS％值分别是(59.6±3.1)、(55.6±2.2)、(48.4±1.4)、(35.5±1.7)、(57.9±2.0)、(52.2±2.4)、(50.3±1.2)％和(46.9±2.8)％.芬太尼后处理和肢体远隔缺血后处理可显著降低心肌缺血/再灌注后的IS％值以及CK-MB和cTnI活性,联合应用芬太尼后处理和肢体远隔缺血后处理可获得显著增强的心肌保护效果.NTD可显著削弱肢体远隔缺血后处理的心肌保护作用,但对芬太尼后处理的心肌保护作用无影响.预先应用NTD能够消除联合应用芬太尼后处理和肢体远隔缺血后处理在降低IS％值方面的协同作用.结论 δ受体参与肢体远隔缺血后处理的心肌保护作用,但未参与芬太尼后处理的心肌保护作用.δ受体对联合应用芬太尼后处理和肢体远隔缺血后处理在降低心肌梗死面积方面的协同作用十分重要.     

缺血后处理对大鼠离体心脏缺血再灌注损伤的作用

目的探讨缺血后处理对大鼠离体心脏缺血再灌注损伤的作用。方法24只Wistar大鼠,随机分为3组(n=8):正常对照组(C组)、缺血再灌注组(I/R组)、缺血后处理组(IPC组)。采用大鼠离体心脏Langendorff灌流模型,C组用K-H液灌注160min;I/R组全心缺血40 min,再灌注120 min; IPC组全心缺血40 min后,再灌注10 s,缺血10 s,反复6次,然后持续再灌注118 min。测定再灌注15、30、120 min时冠脉流量(CF)及冠脉流出液心肌肌钙蛋白I(cTnI)浓度,再灌注120 min时,取心肌组织,测定丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,电镜下观察心肌细胞超微结构。结果缺血再灌注可导致CF降低,冠脉流出液cTnI浓度升高,心肌SOD活性下降,MDA含量升高,心肌细胞超微结构产生病理学改变,缺血后处理可减弱上述改变。结论缺血后处理减轻脂质过氧化反应,对大鼠离体缺血再灌注心脏产生保护作用。     

缺血后处理对大鼠骨骼肌缺血再灌注损伤的影响

目的 探讨缺血后处理对大鼠骨骼肌缺血再灌注损伤的影响以及应用缺血后处理的时机.方法 将32只大鼠随机分成四组,采用切断患肢全部皮肤、肌肉和神经,保留患肢股动静脉的动物模型,通过夹闭和开放股动静脉造成骨骼肌缺血和再灌注损伤.采用测定骨骼肌缺血4 h.再灌注1 h后血清丙二醛(MDA)、骨骼肌髓过氧化物酶(MPO),再灌注6 h后骨骼肌的死亡程度来观察缺血后处理对大鼠骨骼肌缺血再灌注损伤的影响,以及再灌注5 min后应用缺血后处理是否对骨骼肌缺血再灌注损伤有保护作用.结果 对骨骼肌缺血4 h再灌注6 h的损伤,再灌注开始后即刻应用30 s缺血、30 s再通,三次循环的缺血后处理对骨骼肌的缺血再灌注损伤即有保护作用,不仅减少了骨骼肌再灌注区域中性粒细胞浸润(MPO)和血清氧自由基水平(MDA)水平,而且减少了骨骼肌的死亡程度;再灌注5 min后应用缺血后处理并没有降低骨骼肌缺血再灌注区域的MPO和血清MDA水平,也没有降低骨骼肌缺血再灌注后的死亡程度,与直接缺血再灌注组相同,对骨骼肌缺血再灌注损伤并没有保护作用.结论 骨骼肌缺血后再灌注开始前立刻应用缺血后处理对大鼠骨骼肌缺血再灌注损伤有一定的保护效果,可以减少骨骼肌缺血再灌注损伤后的死亡程度;缺血后处理应用时机非常重要,再灌注5 min后应用缺血后处理则失去对骨骼肌缺血再灌注损伤的保护作用.     

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.     

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.     

Organ protective effects of volatile anesthetics and perioperative outcomes

Anesthetic agents, especially, volatile anesthetics are considered to exert organ toxicity such as nephrotoxicity and hepatotoxicity; however, recent aggressive researches explored the beneficial effects of volatile anesthetics as an organ protectant. Ischemic preconditioning is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the myocardium and brain against prolonged ischemic insult. General anesthesia showed the protection against both ischemic myocardial and brain reperfusion injuries. This phenomenon is called anesthetic preconditioning. Regarding the organ protection, anesthetic preconditioning is one of the useful ways to diverse the organ protective effects not only to heart but also brain. Nowadays, ischemic postconditioning, consisting of repeated brief cycles of ischemia-reperfusion performed immediately after reperfusion following a prolonged ischemic insult, dramatically reduces infarct size in experimental models and such clinical studies are reported. Both preconditioning and postconditioning share the same signal transduction pathway and inhibit the mitochondrial permeability transition (MPT) that leads to either apoptosis or necrosis of myocardium and neuronal cell. Both phenomena look very promising, but we still lack the real evidence for human reserach in terms of the clinical outcome and further analysis is necessary. Neurotoxicities of anesthetic agents are very crucial problems for the patient and they are considered to be due to the activation of IP3 receptor in ER after exposure to volatile anesthetics. Massive release of Ca2+ from ER induces Ca2+ overload leading to mitochondria permeability transition (MPT) and induces apoptosis in the brain or aggravates the neurodegenerative disease. Susceptible mechanisms and beneficial treatment for the toxicity of general anesthesia is considered as a critical subject to discuss and challenge to solve for our future.     

Effects of liraglutide and ischemic postconditioning on myocardial salvage after I/R injury in pigs*

Objectives. Acute STEMI is routinely treated by acute PCI. This treatment may itself damage the tissue (reperfusion injury). Conditioning with GLP-1 analogs has been shown to reduce reperfusion injury. Likewise, ischemic postconditioning provides cardioprotection following STEMI. We tested if combined conditioning with the GLP-1 analog liraglutide and ischemic postconditioning offered additive cardioprotective effect after reperfusion of 45?min coronary occlusion of left anterior descending artery (LAD). Design. Fifty-eight non-diabetic female Danish Landrace pigs (60?±?10kg) were randomly assigned to four groups. Myocardial infarction (MI) was induced by occluding the LAD for 45?min. Group 1 (n?=?14) was treated with i.v. liraglutide after 15?min of ischemia. Group 2 (n?=?17) received liraglutide treatment concomitant with ischemic postconditioning, after 45?min of ischemia. Group 3 (n?=?15) recieved ischemic postconditioning and group 4 (n?=?12) was kept as controls. Results. No intergroup differences in relative infarct size were detected (overall mean 57?±?3%; p?=?0.68). Overall mortality was 34% (CI 25–41%) including 26% post-intervention, with no intergroup differences (p?=?0.99). Occurrence of ventricular fibrillation (VF) was 59% (CI 25–80%) including 39% postintervention with no intergroup differences (p?=?0.65). Conclusions. In our closed-chest pig-model, we were unable to detect any cardioprotective effect of liraglutide or ischemic postconditioning either alone or combined.     

After four hours of cold ischemia and cardioplegic protocol, the heart can still be rescued with postconditioning

BACKGROUND: There is evidence that ischemia lasting more than 4 hours affects cardiac allograft survival. Ischemia and reperfusion are associated with additional deleterious effects. Protective effects of preconditioning are already being used but protocols based on postconditioning have not been evaluated. We tested the impact of postconditioning on hearts maintained in the cold for a long period of total global ischemia and we compared the results with those obtained with pyruvate, a cardioprotective molecule. METHODS: Isolated working rat hearts were subjected to a global total ischemia (4 h/4 degrees C), followed by 45 min of reperfusion. Postconditioning consisted of brief total global ischemia applied three times during the onset of reperfusion (ischemia: 30 sec, reperfusion: 30 sec). Superoxide anion production and collagen content were evaluated on cryosections. RESULTS: Our results showed that postconditioning led to improvements in cardiac functions that were comparable to those conferred by pyruvate. Postconditioning reduced myocardial damage, gave better functional recovery, and better preserved the collagen content. It reduced the duration of arrhythmias at the onset of reperfusion. In the postconditioning group, this improvement was associated with a reduction in superoxide production. CONCLUSIONS: In conclusion, our study showed that postconditioning induced good cardioprotective effects in a long cold (4 hr/4 degrees C) ischemia protocol and led to lower O2 production in part mediated by the reduction in NAPDH oxidase activity. It is interesting to note that, in our experimental conditions, the beneficial effects of postconditioning were comparable to those produced by pyruvate.     

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.     

Volatile anesthetic-induced cardiac preconditioning

Pharmacological preconditioning with volatile anesthetics, or anesthetic-induced preconditioning (APC), is a phenomenon whereby a brief exposure to volatile anesthetic agents protects the heart from the potentially fatal consequences of a subsequent prolonged period of myocardial ischemia and reperfusion. Although not completely elucidated, the cellular and molecular mechanisms of APC appear to mimic those of ischemic preconditioning, the most powerful endogenous cardioprotective mechanism. This article reviews recently accumulated evidence underscoring the importance of mitochondria, reactive oxygen species, and K_ATP channels in cardioprotective signaling by volatile anesthetics. Moreover, the article addresses current concepts and controversies regarding the specific roles of the mitochondrial and the sarcolemmal K_ATP channels in APC.     

缺血后处理对大鼠移植肝缺血再灌注损伤的保护作用

目的探讨在体条件下缺血后处理对大鼠移植肝缺血再灌注损伤的保护作用及其可能机制。方法采用SD大鼠原位肝移植模型,供肝冷保存时间100min,无肝期控制于18min以内,60只雄性健康SD大鼠随机分为3组,对照组12只,缺血再灌注损伤组和后处理组各24只。对照组开腹后仅游离肝周韧带;缺血再灌注损伤组受体大鼠供肝切除前仅以肝素化生理盐水经门静脉灌注;后处理组供肝植入后完全再灌注前,给予多次短暂复灌复停作为缺血后处理。缺血再灌注损伤组、后处理组受体一半（6只）于再灌注后2h留取血液及肝组织,另一半（6只）于再灌注后6h留取肝组织。对照组于关腹后相应时间留取血液及肝组织。各组分别检测肝功能,采用酶联免疫吸附法测定血清肿瘤坏死因子Or．和中性粒细胞弹性蛋白酶。根据酶促反应原理,利用分光光度仪测定肝脏谷胱甘肽过氧化物酶、丙二醛、髓过氧化物酶、超氧化物歧化酶。肝组织HE染色后光镜下观察组织学变化。结果缺血再灌注损伤组和后处理组血清肝功能指标、炎性细胞因子水平及肝组织过氧化物含量均高于对照组（P〈0．05）,而后处理组较缺血再灌注损伤组则明显低（P〈0．05）;缺血再灌注损伤组和后处理组肝组织抗氧化酶活力显著低于对照组（P〈0．05）,而后处理组较缺血再灌注损伤组则明显高（P〈0．05）。结论缺血后处理对大鼠移植肝的缺血再灌注损伤有明显的保护作用。提高组织的抗氧化能力和降低炎性细胞因子水平可能是缺血后处理保护作用的机制之一。