ION HOMEOSTASIS AND METABOLISM IN THE DISEASED HEART-A STUDY USING MULTI-NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

患病心脏中的离子稳态和代谢——多核磁共振波谱研究

• 批准号: 07045051
• 负责人: KUSUOKA Hideo
• 金额: $ 2.69万
• 依托单位: OSAKA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07045051/
• 关键词: MYOCARDIUM; ION HOMEOSTASIS; ISCHEMIA; REPERFUSION; CALCIUM ION; SODIUM ION; STUNNING; NUCLEAR MAGNETIC RESONANCE; 糖尿病; カルシウム・ホメオスタシス; カルシウム・チャネル遮断薬; 核磁気共鳴法

This project aimed to reveal the relation between the abnormalities in ion homeostasis and contractile failure in the models of diseased hearts. The follwing points were clarified in this research project ;1. The relation between the abnormalities in intracellular calcium ion homeostasis and contractile failure in the hearts reperfused after acute ischemia. The transient calcium overload during early phase of reperfusion after a brief period of ischemia activates calcium-dependent protease, and protease disappears myofilament-related skeletal proteins, resulting in contractile failure.2. The mechanism of calcium channel blockers for protection against ischemia/reperfusion injury. Pretreatment of calcium channel blockers prevents calcium overload during ischemia, and protects myocardium against contractile failure induced by ischemia and/or reperfusion. It is clarified that calcium influx from the extracellular space is necessary for the calcium overload during ischemia.3. The relation between the abnormalities in intracellular sodium ion homeostasis during ischemia and contractile failure after reperfusion. Sodium accumulation during ischemia is mediated by sodium influx via Na/H exchanger, and shows significant negative correlation with contractile recovery after reperfusion. Cardiac protection against ischemia in diabetic hearts is caused by the reduced activity of Na/H exchanger. These results indicate that the abnormalities in ion homeostasis is one of major mechanisms for contractile dysfunction in diseased hearts.

本课题旨在揭示心脏病模型中离子稳态异常与收缩功能障碍之间的关系。本研究主要阐明了以下几点：1.急性缺血再灌注心脏细胞内钙离子稳态异常与收缩功能衰竭的关系。短暂缺血后再灌注早期短暂的钙超载激活钙依赖性蛋白酶，蛋白酶使与肌张力相关的骨骼蛋白消失，导致收缩功能衰竭.钙通道阻滞剂对缺血/再灌注损伤的保护机制。钙通道阻滞剂的预处理可防止缺血时的钙超载，并保护心肌免受缺血和/或再灌注引起的收缩衰竭。阐明了细胞外钙离子内流是缺血时钙超载的必要条件.缺血时细胞内钠离子稳态异常与再灌注后心肌收缩衰竭的关系。缺血时钠蓄积是通过Na/H交换器介导的钠内流，并与再灌注后收缩恢复呈显著负相关。在糖尿病心脏中，心脏对缺血的保护是由Na/H交换器活性降低引起的。这些结果表明，离子稳态的异常是疾病心脏收缩功能障碍的主要机制之一。

项目成果

Imahashi K: "Alteration of intracellular Na+ during ischemia in diabetic rat hearts" Journal of Molecular and Cellular Cardiology. 30(in press). (1998)

Imahashi K：“糖尿病大鼠心脏缺血期间细胞内 Na 的变化”《分子与细胞心脏病学杂志》。

Matsumura Y: "Inhomogeneous disappearance of myofilament-related cytoskeletal proteins in stunned myocardium of guinea pig" Circulation Research. 79. 447-454 (1996)

Matsumura Y：“豚鼠震惊心肌中肌丝相关细胞骨架蛋白的不均匀消失”循环研究。