Pathogenesis and protection of ischemia and reperfusion injury in myocardium.
Pathogenesis and protection of ischemia and reperfusion injury in myocardium.
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DOI：
10.1272/jnms.70.384
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发表时间：
2003-10-01
影响因子：
1
通讯作者：
Sugisaki, Yuhichi
中科院分区：
文献类型：
--
作者：
Asano, Goro;Takashi, En;Sugisaki, Yuhichi
影响缺血性心脏病变进展的重要因素是血流状态和心脏代谢异常。心肌缺血是由氧需求增加或氧供应不足引起的。Na ~+-Ca ~（++）离子交换机制在心肌收缩和细胞损伤中起重要作用。Na ~+ - K ~+ ATP酶和Ca ~（++）-ATP酶在组织化学上定位于肌膜下池、肌膜网和毛细血管内皮，维持心肌功能。这些ATP酶受到缺氧、超氧化物和自由基的损害。O2的还原导致超氧化物和过氧化氢（H2 O2）的产生。H2 O2是高度扩散性的，并诱导细胞损伤。H2 O2似乎不仅影响脂质，而且还影响嵌入细胞膜的膜内蛋白。羟基自由基（OH）也参与脂质过氧化。在缺血性和/或再灌注心脏病的发病机制中，缺血诱导所有膜系统的快速或逐渐变化，并引起可逆或不可逆的损伤，包括坏死和凋亡性细胞死亡。糖基化终末产物（AGEs）的积累是糖尿病性心肌病的重要病因之一。AGEs蛋白影响细胞变化，如数量增加、转化、功能紊乱和细胞因子消除。在冠状动脉中，平滑肌细胞的迁移是由AGEs蛋白通过受体（AGEs）和细胞因子释放引起的。AGEs的积累可能通过血管内皮细胞介导糖尿病大血管病变，血管内皮细胞表达AGEs的水平增加可能是糖尿病加速动脉粥样硬化的原因之一。另一方面，我们也报道了高血糖是糖尿病动物缺血性心脏损伤的促进因素。缺血预适应是一种有效的心肌保护机制。本文着重研究了蛋白激酶C（PKC）、丝裂原活化蛋白激酶（MAPK）和线粒体ATP依赖性钾通道（mitoKATP）作为细胞适应所必需的介质或终末效应器。mitoKATP通道的开放诱导线粒体的去极化，减少再灌注期间的Ca++过载。使用胚胎干细胞证实了心肌细胞的再生。表现出自搏动的心肌细胞由骨髓中胚层组织中的间充质干细胞产生。
The important factors that influence the progress of ischemic cardiac lesion are blood flow condition and abnormal cardiac metabolism. Myocardial ischemia is promoted by either an increase in oxygen demand or a shortage of oxygen supply. The Na+-Ca++ ion exchange mechanism is very important for myocardial contraction and cell damage. Na+ - K+ATPase and Ca++ ATPase are enzyme histochemically localized in subsarcolemmal cisterns, sarcolemmal reticulum and capillary endothelium, and keep myocardial function. These ATPases are impaired by anoxia, superoxides and free radicals. The reduction of O2 results in the production of superoxides as well as hydrogen peroxide (H2O2). H2O2 is highly diffusible and induces cell damage. H2O2 appears to affect not only lipids but also intramembranous proteins embedded in the cell membrane. The hydroxyl radical (OH) also participates in lipid hyperoxidation. In the pathogenesis of ischemic and/or reperfused heart disease, ischemia induces rapid or gradual changes in all membrane systems and causes reversible or irreversible injury including necrotic and apoptotic cell death. Advanced glycation end products (AGEs) accumulation induced by diabetic conditioning is an etiologic factor inducing cardiomyopathy. The AGEs protein affects cell changes such as increased number, transformation, functional disturbance and cytokine elimination. In coronary arteries, the migration of smooth muscle cells caused by the taking up of AGEs proteins through the receptor (RAGE), and cytokine discharge are suggested. AGEs accumulation may induce diabetic macroangiopathy through RAGE, and the increase in the level of RAGE expression by endothelial cells could be a reason that diabetes mellitus accelerates atherosclerosis. On the other hand, we also reported that hyperglycemia was a promoting factor of ischemic heart injury in diabetic animals. Ischemic preconditioning is a useful phenomenon that limits myocardial damage. We foused on protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and mitochondrial ATP-dependent potassium (mitoKATP) channel as mediator or end which effector are necessary for adaptation. The opening of the mitoKATP channel induces the depolarization of mitochondria, reducing Ca++ overload during reperfusion. The regeneration of myocardial cells is confirmed using embryonic stem cells. Myocardial cells that exhibit self-pulsation are generated from mesenchymal stem cells in mesodermal tissues of the bone marrow.