Cardioprotection in an in vitro model of hypoxic preconditioning.
Cardioprotection in an in vitro model of hypoxic preconditioning.
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DOI：
10.1016/s0022-2828(08)80041-7
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发表时间：
1995
影响因子：
5
通讯作者：
K. Webster;D. J. Discher;N. Bishopric;N. Bishopric
中科院分区：
文献类型：
--
作者：
K. Webster;D. J. Discher;N. Bishopric;N. Bishopric
在实验动物和人类中，短时间的心肌缺血似乎提供了对随后延长的缺血发作的保护。这种现象被称为缺血预适应，目前还没有在细胞或分子水平上描述这种现象；然而，组织缺氧似乎是必需的。在这项研究中，我们使用了先前发展的低氧心肌细胞培养方法，以建立细胞培养中缺血(或低氧)预适应的模型。通过花生四烯酸加成释放和收缩恢复实验，我们证明，培养的新生大鼠心肌细胞在低氧25分钟后复氧预适应后，可在长达6小时的持续严重低氧中保护心肌细胞免受膜损伤。未预适应的心肌细胞在2~4h后表现出明显的低氧损伤，PMA(一种促肿瘤的佛波酯)可模拟低氧预适应的保护作用，而M胆碱能激动剂卡巴胆碱对心肌细胞无保护作用。我们的数据表明，培养中分离的心肌细胞仍有能力接受低氧预适应，这一途径可能涉及蛋白激酶C的激活。
Short periods of myocardial ischemia appear to provide protection against subsequent prolonged ischemic episodes in experimental animals and in man. This phenomenon, known as ischemic preconditioning, has not yet been characterized at the cellular or molecular levels; however, tissue hypoxia appears to be required. In this study, we used a previously developed method for hypoxic cardiac myocyte culture in order to establish a model for ischemic (or hypoxic) preconditioning in cell culture. We demonstrate that cultured neonatal rat cardiac myocytes preconditioned by 25 min of exposure to hypoxia followed by reoxygenation were protected against membrane damage for up to 6 h of prolonged severe hypoxia, as determined by arachidonic add release and contractile recovery. In contrast, non-preconditioned myocytes exhibited significant hypoxic damage after 2-4 h. Pretreatment of cells with PMA, a tumor-promoting phorbol ester, mimicked the protective effects of hypoxic preconditioning; pretreatment with the muscarinic cholinergic agonist carbachol had no effect. Our data suggests that isolated myocytes in culture remain competent to be preconditioned by hypoxia, through a pathway that may involve the activitation of protein kinase C.