链脲佐菌素诱导的糖尿病大鼠心脏缺血预处理后的能量代谢

Energy metabolism after ischemic preconditioning in streptozotocin-induced diabetic rat hearts.

作者信息

Tatsumi T, Matoba S, Kobara M, Keira N, Kawahara A, Tsuruyama K, Tanaka T, Katamura M, Nakagawa C, Ohta B, Yamahara Y, Asayama J, Nakagawa M

机构信息

Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.

出版信息

J Am Coll Cardiol. 1998 Mar 1;31(3):707-15. doi: 10.1016/s0735-1097(97)00556-1.

DOI:10.1016/s0735-1097(97)00556-1

PMID:9502657

Abstract

OBJECTIVES

The aim of this study was to compare the cardioprotective effects of preconditioning in hearts from streptozotocin-induced diabetic rats with its effects in normal rat hearts.

BACKGROUND

The protective effect of ischemic preconditioning against myocardial ischemia may come from improved energy balance. However, it is not known whether preconditioning can also afford protection to diabetic hearts.

METHODS

Isolated perfused rat hearts were either subjected (preconditioned group) or not subjected (control group) to preconditioning before 30 min of sustained ischemia and 30 min of reperfusion. Preconditioning was achieved with two cycles of 5 min of ischemia followed by 5 min of reperfusion.

RESULTS

In the preconditioned groups of both normal and diabetic rats, left ventricular developed pressure, high energy phosphates, mitochondrial adenosine triphosphatase and adenine nucleotide translocase activities were significantly preserved after ischemia-reperfusion; cumulative creatine kinase release was smaller during reperfusion; and myocardial lactate content was significantly lower after sustained ischemia. However, cumulative creatine kinase release was less in the preconditioned group of diabetic rats than in the preconditioned group of normal rats. Under ischemic conditions, more glycolytic metabolites were produced in the diabetic rats (control group) than in the normal rats, and preconditioning inhibited these metabolic changes to a similar extent in both groups.

CONCLUSIONS

The present study demonstrates that in both normal and diabetic rats, preservation of mitochondrial oxidative phosphorylation and inhibition of glycolysis during ischemia can contribute to preconditioning-induced cardioprotection. Furthermore, our data suggest that diabetic myocardium may benefit more from preconditioning than normal myocardium, possibly as a result of the reduced production of glycolytic metabolites during sustained ischemia and the concomitant attenuation of intracellular acidosis.

摘要

目的

本研究旨在比较链脲佐菌素诱导的糖尿病大鼠心脏预处理的心脏保护作用及其在正常大鼠心脏中的作用。

背景

缺血预处理对心肌缺血的保护作用可能源于能量平衡的改善。然而，尚不清楚预处理是否也能对糖尿病心脏起到保护作用。

方法

在持续缺血30分钟和再灌注30分钟之前，将离体灌注的大鼠心脏分为预处理组（进行预处理）和对照组（未进行预处理）。预处理通过两个5分钟缺血后再灌注5分钟的周期实现。

结果

在正常和糖尿病大鼠的预处理组中，缺血再灌注后左心室舒张末压、高能磷酸盐、线粒体三磷酸腺苷酶和腺嘌呤核苷酸转位酶活性均得到显著保留；再灌注期间肌酸激酶的累积释放量较小；持续缺血后心肌乳酸含量显著降低。然而，糖尿病大鼠预处理组的肌酸激酶累积释放量低于正常大鼠预处理组。在缺血条件下，糖尿病大鼠（对照组）产生的糖酵解代谢产物比正常大鼠多，且预处理在两组中对这些代谢变化的抑制程度相似。