Efforts to prevent ischemic injury

Efforts to prevent ischemic injury have focussed on finding ways to block events associated with irreversible ischemic injury. In 1986, Murrey et al described a classic phenomenon termed ischemic preconditioning (IPC) for the first time. It was originally thought that each ischemic episode caused cumulative ATP depletion while the intermittent reperfusion would wash out the ischemic catabolites.Surprisingly ATP levels were not depleted by subsequent ischemic challenges and no infarction occurred. This observation led the same group of scientists to test the hypothesis that the preservation of high-energy phosphates was due to a slowing of consumption during ischemia associated with a rapid and protective adaptation of the myocyte. They tested this hypothesis by subjecting the myocardium to a series of four 5-min coronary branch occlusions; each separated by 5 min of reperfusion. This rendered the myocardium more resistant to the subsequent sustained 40-min ischemic insult. The infarct size was reduced to 25 % of that seen in control group. This phenomenon is called preconditioning with ischemia.
Preconditioning of the myocardium with short episodes of sublethal ischemia will delay the onset of necrosis during a subsequent lethal ischemic insult. It has also been shown that the protective effect of IPC is thought to be stimulated by local action of adenosine, opiates and bradykinin which are all endogenously released by ischemic cells. They activate G-protein coupled pathways, which carries a protective signal to an end-effector. There have been many suggestions to what this might be, the sarcolemmal ATP-sensitive potassium channel, the mitochondrial ATP-sensitive potassium channel, the mitochondrial permeability transition pore, reactive oxygen species generation. Ischemic preconditioning seems to involve a variety of stress signals which include activation of membrane receptors and signaling molecules such as protein kinase C, mitogen-activated protein kinases, opening of ATP-sensitive potassium channel, and expression of many protective proteins.

結果 (中文) 1:

努力防止缺血性损伤，集中于找到块与不可逆的缺血性损伤相关联的事件的方法。1986 年，马锐 et al 描述了一个典型的现象，称为缺血预处理 (IPC) 第一次。它原本以为每个缺血性发作造成累积 ATP 耗竭，而间歇灌注会洗出缺血性的降解产物。令人惊讶 ATP 水平不已经用尽了所有随后的缺血性挑战和没有梗死发生。这种观察领导的同一集团的科学家来测试的假设，即保存的高能磷酸盐是由于心肌缺血与心肌细胞快速和保护适应消费放缓。他们测试这一假设使心肌遭受一系列的四个 5 分钟冠状动脉分支闭塞;彼此相隔 5 分钟的再灌注。这呈现更耐随后持续 40 分钟缺血心肌。心肌梗死面积被降低到 25%，在对照组中看到。这种现象称为缺血预处理。与短片段的亚致死缺血预处理的心肌会延缓坏死在随后的致命缺血性侮辱。它也显示，IPC 的保护作用认为，以刺激地方行动腺苷、 鸦片制剂、 缓激肽所有内在发布由缺血的细胞。他们激活 G 蛋白耦合途径，运载到末端的保护信号。一直到这个可能是什么，细胞膜 ATP 敏感性钾通道，线粒体 ATP 敏感性钾通道，线粒体膜通透性转换孔，活性氧生成的很多建议。缺血预处理似乎涉及到各种应力信号包括激活的膜受体和蛋白激酶 C、 丝裂原活化蛋白激酶、 ATP 敏感性钾通道开放和很多保护性蛋白表达的信号分子。

結果 (中文) 3:

预防缺血性脑损伤的努力集中在寻找与不可逆性缺血损伤相关的事件的方法。1986，马锐等人描述了一个经典的现象称为缺血预处理（IPC）首次。原本以为每个缺血发作引起的累积ATP耗竭而间歇灌注洗掉缺血代谢产物。令人惊讶的是，在随后的缺血再灌注的挑战和没有梗死发生，令人惊讶的。这一观察LED这个科学家小组测试假说，缺血的快速保护心肌细胞适应相关的在保存高能磷酸盐是由于放缓的消费。他们对心肌的一系列四分钟的冠状动脉分支闭塞测试这一假说；每相隔5分钟再灌注。这使得心肌更耐，随后持续40分钟的缺血侮辱。对照组心肌梗死面积减少到25%。这种现象被称为缺血预处理。在短暂的非致死心肌缺血预处理延迟坏死发病随后的致死性缺血损伤。它也表明，IPC的保护作用 认为是由 腺苷局部作用刺激，鸦片和 缓激肽 都  缺血性细胞释放的内源性。他们  耦合途径激活G蛋白，对末端执行器进行保护的信号。已经有很多的建议，这可能是什么，这 膜 ATP敏感钾通道，线粒体ATP敏感性钾通道，这 线粒体通透性转换孔， 活性氧 代。缺血预处理似乎涉及到各种各样的应力信号，其中包括激活膜受体和信号分子，如蛋白激酶，有丝分裂原激活蛋白激酶，开放的敏感钾通道，和许多保护蛋白的表达。