Park J W, Chun Y S, Kim M S, Park Y C, Kwak S J, Park S C
Department of Pharmacology, Heart Research Institute, Seoul National University College of Medicine, Republic of Korea.
Int J Cardiol. 1998 Jul 1;65(2):139-47. doi: 10.1016/s0167-5273(98)00117-x.
Ischemia-reperfusion heart injury is an important pathologic condition against which many strategies, mainly involving antioxidants or radical scavengers, have been developed, but without satisfactory results. In the present experiment, modulation of the cytosolic NADH/NAD ratio by pyruvate and aspartate was tested in order to protect the heart from ischemia-reperfusion injury.
Effects of pyruvate and aspartate on cardiac function recovery and redox potential were analyzed in the isolated heart of male Sprague-Dawley rats. Hearts were made globally ischemic for 20 min and then reperfused for 30 min.
Pyruvate and aspartate protected against tissue injury and improved contractile function after reperfusion of ischemic hearts, and these substances effectively decreased the tissue and cytosolic NADH/NAD ratio of the myocardium in a dose-dependent manner. Postischemic cardiac functions were negatively related to tissue and cytosolic NADH/NAD ratios. Increased NADH selectively inhibited myocardial xanthine dehydrogenase in vitro. It was thus expected that a decrease of NADH might limit the production of reactive oxygen species through the recovery of xanthine dehydrogenase activity.
These results indicate that a decrease of NADH is related to pyruvate and aspartate-induced protection of ischemic myocardium.
缺血再灌注性心脏损伤是一种重要的病理状况，针对此状况已开发出许多策略，主要涉及抗氧化剂或自由基清除剂，但结果并不理想。在本实验中，测试了用丙酮酸和天冬氨酸调节胞质NADH/NAD比率，以保护心脏免受缺血再灌注损伤。
在雄性Sprague-Dawley大鼠的离体心脏中分析丙酮酸和天冬氨酸对心脏功能恢复和氧化还原电位的影响。使心脏整体缺血20分钟，然后再灌注30分钟。
丙酮酸和天冬氨酸可防止缺血心脏再灌注后的组织损伤并改善收缩功能，并且这些物质以剂量依赖的方式有效降低了心肌的组织和胞质NADH/NAD比率。缺血后心脏功能与组织和胞质NADH/NAD比率呈负相关。增加的NADH在体外选择性抑制心肌黄嘌呤脱氢酶。因此，预计NADH的减少可能通过恢复黄嘌呤脱氢酶活性来限制活性氧的产生。
这些结果表明，NADH的减少与丙酮酸和天冬氨酸诱导的对缺血心肌的保护作用有关。
