糖尿病时KATP通道对心肌缺血预适应的影响

糖尿病时心脏KATP通道活性的降低或消失，可能是影响糖尿病患者心肌缺血预适应保护作用的重要原因。糖尿病时KATP通道基因突变、晚期糖基化终末产物生成增多、能量代谢紊乱、一氧化氮生成减少等均可导致该通道活性或数量的降低。全面了解糖尿病时KATP通道改变的机制，对进一步探寻糖尿病心血管并发症新疗法具有重要意义。     

对KATP通道介导缺血预适应心肌再灌注损伤的研究

目的探讨优降糖对KATP通道介导心肌缺血预适应作用的影响。方法将44只大鼠随机分为心肌缺血预适应组(IPC组)、优降糖组(GLI组)、优降糖 IPC组(G-P组)和对照组(C组)。心肌缺血预适应由3次10min缺血/10min再灌注组成。所有大鼠均接受30min缺血/60min再灌注。梗死范围由饱和曲利本蓝和红四氮唑蓝染色判定,并以坏死区占缺血区的百分率表示。Ⅱ导联记录心脏室性心律失常。结果IPC能显著缩小缺血/再灌注后的心肌梗死范围,且这种作用能被KATP通道阻滞剂优降糖完全取消。IPC可减少缺血/再灌注所致的室性心律失常的发生,但这种保护作用不能被优降糖所阻断。结论优降糖对KATP介导IPC的心肌保护作用有影响。     

ATP敏感性钾通道在缺血预适应中的作用

缺血预适应对心肌缺血/再灌注损伤有一定的保护作用,而ATP敏感性钾通道（KATP）是缺血预适应的重要环节。KATP开放剂可以产生预适应样心肌保护作用,KATP阻断剂能取消缺血预适应的保护作用。但KATP介导缺血预适应的作用位点是在心肌细胞膜还是在线粒体尚有争议。作者就KATP的结构,功能和在缺血预适应中的作用与机制作一综述。     

实验性家兔缺血预适应减轻心肌细胞凋亡

为探讨缺血预适应在预防或减轻心肌损伤和心肌细胞凋亡中的作用,制备了家兔缺血预适应、缺血－再灌注损伤和持续缺血模型,并采用末端脱氧核苷酸转换酶介导的生物素平移缺口末端标记技术检测心肌细胞凋亡情况;同时观察外周血心肌酶、氧自由基等水平。结果发现,再灌注损伤组和持续缺血组血清心肌酶含量明显高于正常组和无显著差异（Ｐ〉０．０５）;同时,前两组的血浆过氧化物歧化酶活性明显降低（Ｐ〈０．０１）,而在正常组和缺     

缺血预适应研究进展

缺血预适应研究进展（ＬａｗｓｏｎＣＳ，Ｄｏｗｎｅｙ．ＣａｒｄｉｏｖａｓｃＲｅｓ，１９９３，２７：５４２（英文）〕缺血预适应（ｐｒｅｃｏｎｄｉｔｉｏｎｉｎｇ）是指在短暂缺血之后心肌迅速产生一种自我保护状态，对随后较长时间缺血的耐受性明显增强。目前实验证...     

细胞骨架在原代培养乳鼠窦房结细胞模拟缺血预适应中的作用研究

观察细胞骨架在乳鼠窦房结细胞模拟缺血预适应(IP)中的作用。取培养 2d的乳鼠窦房结细胞,随机分为①对照组;②模拟缺血 /再灌注(I/R)组;③模拟IP组;④phalloidin(微丝聚合剂 ) +I/R组;⑤cytochalasinD(微丝解聚剂) +IP组:⑥Taxol(微管聚合剂 ) +I/R组;⑦colchicine(微管解聚剂 ) +IP组。以FITC phalloidin及SABC cy3试剂盒分别标记F actin及β tubulin,用激光共聚焦显微镜检测各组窦房结细胞荧光强度改变。结果:①phalloi din预处理能显著增强再灌注后窦房结细胞F actin及β tubulin的荧光强度,并维持其形态、结构的相对完整性,模拟IP效应。②cytochalasinD及colchicine均能阻断模拟IP的细胞骨架保护作用,显著降低窦房结细胞F actin及β tubulin的荧光强度,导致细胞骨架的解体。③Taxol未能对I/R窦房结细胞提供IP样保护作用。结论:维持微丝结构的相对完整性可以减轻窦房结细胞I/R损伤,模拟IP效应;维持细胞骨架的相对完整性是IP产生的重要前提。     

浅论缺血预适应

浅论缺血预适应牟善初缺血预适应（ｉｓｃｈｅｍｉｃｐｒｅｃｏｎｄｉｔｉｏｎｉｎｇ）或称缺血预处理，是１９８６年Ｍｕｒｒｙ、Ｒｅｉｍｅｒ、Ｊｅｎｎｉｎｇｓ等提出的概念。他们在动物的心肌缺血性损伤试验中发现，如果先造成多次短暂的缺血（阻断冠状动脉回旋支每次...     

心肌的缺血预适应现象

<正> 有效地限制急性心肌梗塞范围,是治疗心肌梗塞和提高存活率的重要措施.随着溶栓治疗和冠脉搭桥及成形术的发展,成功地恢复了缺血心肌的血流灌注.晚近发现的心肌缺血预适应现象,是一种心肌自我保护机制,它业已引起人们的广泛关注.围绕心肌缺血预适应这一重要发现展开的基础与临床研究,为有效地改善心肌供血开辟了一条新途径,本文就心肌缺血预适应的研究作一概述.     

缺血预适应的血管内皮保护作用及机制

缺知预适应能显著地减轻缺血再灌注等因素所致冠状动脉内皮、外周血管内皮和培养的内皮细胞损伤。缺血预适应的血管财皮保护可能是其保护缺血心肌的重要机制之一。缺血预适应的血管内皮保护机制是通过释放内源性血管活性物质所介导。     

心肌的缺血预适应及其对心脏的保护作用

短暂的心肌缺血可使心肌快速适应，减少随后较长时间缺血引起的心肌梗塞范围和心律失常发生率。通过腺苷Ａ１受体作用于抑制性Ｇ蛋白，开放三磷酸腺苷敏感钾通道可能是其主要机制。利用心肌的这一内在保护能力，可望提供心肌缺血后延缓心肌梗塞发展，减少致死性心律失常发生，保存心肌收缩功能的新型防治手段。     

Myocardial Ischemic Tolerance Following Heat Stress Is Abolished by ATP-Sensitive Potassium Channel Blockade

Heat stress is known to confer protection against ischemia, but the mechanisms involved are yet to be elucidated. Opening of ATP-sensitive potassium (K_ATP) channels has been demonstrated to be involved in other endogenous forms of cardioprotection, in particular“classic” ischemic preconditioning and delayed preconditioning following treatment with the endotoxin derivative, monophosphoryl lipid A. We therefore speculated that there may be a role for K_ATPchannels in delayed heat stress–induced cardioprotection. This hypothesis was investigated in an in vivo rabbit model of acute myocardial infarction using two structurally dissimilar K_ATP channel blockers, glibenclamide and sodium 5-hydroxydecanoate. Sodium pentobarbitone–anesthetized rabbits were subjected to either transient heat stress at 42 ± 0.2°C for 15 minutes or sham anesthesia. Twenty-four hours later, animals were reanesthetized (“Hypnorm” and sodium pentobarbitone) and a midline sternotomy and pericardiotomy were performed. An anterolateral branch of the circumflex coronary artery was occluded for 30 minutes and reperfused for 2 hours. The infarct-to-risk ratio was significantly limited in vehicle-treated rabbits from 41.3 ± 4.0% in controls (n = 10) to 24.1 ± 5.0% (n = 9; P = 0.014 by one-factor ANOVA) in heat-stressed hearts. This limitation in infarct size was abolished by 0.3 mg/kg iv glibenclamide or 5 mg/kg iv5-hydroxydecanoate when administered 10 minutes prior to coronary occlusion (45.2 ± 6.4%; n = 9 and 41.5 ± 5.0%; n = 5, respectively.) The same doses of glibenclamide and 5-hydroxydecanoate in sham-anesthetized hearts had no effect (42.3 ±5.1%; n = 10 and 51.9 ± 2.2%; n = 6, respectively). The adequacy of the heat stress protocol was confirmed by Western blot analysis of the inducible 72-kD heat stress protein. It is concluded, therefore, that K_ATP channels appear to play a role in the heat stress response. The underlying mechanisms involved are, however, unclear. This revised version was published online in July 2006 with corrections to the Cover Date.     

心肌缺血预适应引起的ATP敏感性钾电流变化

许多研究证实三磷酸腺苷敏感性钾电流 (KATP)在心肌保护的机制中起重要作用 ,但尚未有缺血预适应 (IPC)期间KATP电流变化的直接报道。本实验用全细胞膜片钳技术在豚鼠心室肌细胞上观察了多次模拟缺血 (低氧、去能量 )和再灌注期间KATP电流的变化情况。结果 :对照组 (n =9)和IPC组 (n =12 )的KATP电流分别由实验开始时的- 97± 14和 - 94± 16pA开放至第 3次短暂缺血结束时的 - 5 7± 10和 - 16± 2 0pA(P <0 .0 5 ) ,以及持续缺血 5min时的 35± 2 3和 472± 310pA(P均 <0 .0 1) ;然而在持续缺血晚期和再灌注过程中KATP通道的开放程度在两组之间无显著差异。以上这些效应可被优降糖阻断。结论 :本文首次直接观察到IPC可导致KATP通道在预适应末及随后长时间缺血早期的适度激活 ,但不影响长时间缺血晚期和再灌注过程中的开放程度 ,为进一步研究IPC的发生机制和开发KATP开放剂作为新型抗缺血性心脏病药物提供了理论基础     

Comparison of the Protective Effects of a Highly Selective ATP-Sensitive Potassium Channel Opener and Ischemic Preconditioning in Isolated Human Atrial Muscle

The ATP-sensitive K+ channel (KATP channel) has been implicated in the mechanism of ischemic preconditioning. We compared the protective effects of ischemic preconditioning and a highly selective KATP channel opener, BMS 180448, in human myocardium. BMS 180448 was either used alone or in combination with the KATP channel blocker glibenclamide. Human atrial trabeculae derived from the right atrial appendage were suspended in an organ bath, superfused with oxygenated Tyrode's solution at 37°C, and paced at 1 Hz. Experimental groups (n = 6 in each) were as follows: (1) control (C)—90 minutes hypoxic substrate-free perfusion at 3 Hz (simulated ischemia), followed by 120 minutes of reoxygenation with substrate at 1 Hz (reperfusion); (2) preconditioning (PC)—3 minutes simulated ischemia, 7 minutes reperfusion, followed by 90 minutes simulated ischemia and 120 minutes reperfusion; (3) BMS 180448 (BMS)—exposure to the drug for 5 minutes prior to 90 minutes simulated ischemia and 120 minutes reperfusion; (4) BMS 180448 + glibenclamide (BMS + G)—glibenclamide exposure for 10 minutes, and BMS for 5 minutes prior to 90 minutes simulated ischemia and 120 minutes reperfusion. Force of contraction prior to the commencement of the protocol was assigned the arbitrary value of 100%. Percentage recovery of contractile function at 120 minutes reperfusion was used as the endpoint. BMS (59.2 ± 8.6%) and preconditioning (50.5 ± 3.6%) produced a similar degree of recovery of function at the end of 120 minutes of reperfusion; this was significantly different from the untreated control group (20.8 ± 3.5%, p > 0.05, ANOVA). When glibenclamide was added prior to BMS, protection was lost (20.5 ± 2.7%). In this human atrial preparation, a highly selective KATP channel opener mimicked the protective effect of ischemic preconditioning. This protective effect of BMS was abolished by glibenclamide. These findings confirm that the mechanism of ischemic preconditioning in human muscle may be mediated via opening of the KATP channel.     

一氧化氮与心肌缺血预适应

缺血预适应 (ischemicpreconditioning ,IPC)是一种多元性细胞防御现象 ,即经过短暂的缺血刺激 ,使心脏对随后类似的刺激产生保护作用[1] 。这种作用在缺血后数分钟即可出现 (第一保护窗口 ) ,持续时间不足 3小时 ;2 4小时后又出现一次较长的保护作用 (第二保护窗口 ) ,可持续 3～ 4天 ,有助于防止发生心肌顿抑或心肌梗死 ,因此有重要的临床意义[2 ] 。已有大量研究证明 ,这种保护作用与内源性一氧化氮 (NO)有关 ,并指出NO在此保护过程中担任双重角色 ,起初起触发作用 ,随后在整个过程中起调节作用。本文就NO在心肌缺血预适应中的作用作…     

心肌缺血预适应延迟相的研究进展

心肌缺血预适应(ischemicpreconditioning,IPC)现象的发现,为心肌缺血再灌注损伤的预防开拓了一个新的研究领域。IPC分为快速相和延迟相,快速相IPC对心脏具有显著的保护作用,但这种保护作用在IPC后1~2h即消失。延迟相IPC在IPC后24h出现,心脏保护持续时间长,保护范围广。现对IPC延迟相的机制进展作一简要综述。     

心肌缺血预适应中的离子通道

缺血预适应调动机体内源性抗损伤能力，保护缺血缺氧的组织细胞，是近年来心血管领域研究的热点之一。本该对心肌缺血预适应中的离子通道、三磷酸腺苷敏感性钾通道（KATP通道）、L-型钙道道（L-Ca^2 通道）、体积调节性氯通道（Cl vol通道）的特性、作用及其机制作一综述。     

心肌缺血预适应的心脏保护机制研究进展

心肌缺血预适应是指反复短暂的心肌缺血/再灌注可以耐受心肌组织后续更长时间缺血再灌注损伤的现象。它的信号传导途径包括“触发物质-中介物质-效应物质”,最后通过效应物质保护再灌注心肌。     

神经型一氧化氮合酶在小鼠心肌缺血预处理中的作用

目的 应用神经型一氧化氮合酶(nNOS)基因敲除小鼠和nNOS抑制剂,探讨nNOS对心肌缺血预处理后心肌细胞凋亡的影响.方法 实验分为野生型缺血再灌注组(WT IR)、野生型缺血预处理组(WT IP)、野生型缺血预处理L-VNIO处理组(WT IP+ L-VNIO)、基因敲除鼠缺血再灌注组(KO IR)和基因敲除鼠缺血预处理组(KO IP).采用冠状动脉左前降支结扎法建立小鼠缺血再灌注损伤模型,缺血再灌注组缺血30 min再灌注3h,缺血预处理组分别经缺血5 min再灌注5 min连续三个循环后,再缺血30 min再灌注3h,观察TUNEL染色和Caspase-8、Caspase-9、Caspase-3的活性变化,并用Western Blot法观察Bax、Bcl-2和Fas蛋白的表达情况.结果 与WT IR组相比,WT IP组小鼠TUNEL阳性细胞数目减少,Caspase-8、Caspase-9和Caspase-3活性降低,Bax和Fas蛋白表达显著降低,Bcl-2表达显著增加(P＜0.05).而在KO IP组,与KO IR组相比,TUNEL阳性细胞数目和Caspase活性显著增加,Bax和Fas表达显著增高,Bcl-2表达显著降低(P＜0.05).结论 nNOS在心肌缺血预处理时发挥抑制心肌细胞凋亡的作用.     

心肌冬眠、心肌顿抑和缺血预适应在临床中的应用

心肌缺血并不意味着心肌已经发生了不可逆性坏死 ,近来证实缺血心肌组织中至少存在三种重要的缺血性适应 :心肌冬眠、心肌顿抑和缺血预适应。心肌冬眠是心肌对长期低血流灌注做出的心脏收缩减弱的反应状态。心肌顿抑是短暂缺血血流恢复后仍存留的心肌收缩功能障碍的现象。缺血预适应是一种内源性的自我保护机制 ,是指反复缺血后心肌对缺血的耐受力增加的现象。冬眠和顿抑心肌仍然是存活的 ,应及早识别并采取积极的措施 ,挽救这部分尚存活的心肌 ,尽可能发挥缺血预适应的心肌保护作用 ,改善缺血性心脏病患者的预后