Miwa-Nishimura N, Kanaide H, Abe S, Nakamura M
Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Int J Exp Pathol. 1990 Oct;71(5):727-39.
We made use of the xanthine oxidase inhibitor allopurinol and examined changes related to myocardial injury of the rat heart during hypoxia-re-oxygenation. The rat heart was perfused using the Langendorff method. With low-oxygen perfusion for 60 min in a solution saturated with mixed gases of 95% N2 + 5%O2, contractile tension did not develop and tension development was not restored upon re-oxygenation. During hypoxia, the resting tension increased (4.1 g) in the absence of allopurinol. In the allopurinol-administered group (100 microM), contractile tension did not develop during hypoxia; however, the development of tension was restored (18%) upon re-oxygenation. The elevation of resting tension was less (3.2 g) during hypoxia. All events related to the myocardial injury (inhibition of Na+, K(+)-ATPase activities, generation of malondialdehyde, extracellular leakage of creatine kinase) after low-oxygen perfusion for 60 min and re-oxygenating perfusion for 30 min were mild in the allopurinol treated group, compared with findings in the non-administered group. Tissue ATP at 10 min after low-oxygen perfusion was of a significantly high value in the allopurinol treated group (13.2 mumols/g dry weight), compared with findings in the group not given the drug (8.4 mumol/g dry weight). Sixty minutes after low-oxygen perfusion, tissue ATP in the allopurinol group also remained high, compared with the group not given the drug. Although the intensity of the epicardial NADH fluorescence indicated that the extent of inhibition of aerobic energy production during 10 min of low-oxygen perfusion was the same for both groups, lactate was produced in large quantities in the allopurinol treated group, hence energy generation advanced with glycolysis. These observations suggest that allopurinol prevents myocardial injury as a result of hypoxia-re-oxygenation. In the low-oxygen perfusion period, generation of energy is maintained and improved with glycolysis and there is a reduction in the generation of free radicals and an inhibition in lipid peroxidation.
我们使用黄嘌呤氧化酶抑制剂别嘌呤醇，研究了大鼠心脏在缺氧-复氧过程中与心肌损伤相关的变化。采用Langendorff法灌注大鼠心脏。在含95% N₂ + 5%O₂混合气体饱和的溶液中进行60分钟的低氧灌注时，收缩张力未产生，复氧时张力也未恢复。在缺氧期间，未使用别嘌呤醇时静息张力增加（4.1 g）。在给予别嘌呤醇（100 microM）的组中，缺氧期间收缩张力未产生；然而，复氧时张力恢复（18%）。缺氧期间静息张力的升高较少（3.2 g）。与未给药组相比，在进行60分钟低氧灌注和30分钟复氧灌注后，别嘌呤醇治疗组中所有与心肌损伤相关的事件（Na⁺、K⁺-ATP酶活性抑制、丙二醛生成、肌酸激酶细胞外漏）均较轻。与未给药组（8.4 mumols/g干重）相比，低氧灌注10分钟后别嘌呤醇治疗组的组织ATP值显著较高（13.2 mumols/g干重）。低氧灌注6分钟后，与未给药组相比，别嘌呤醇组的组织ATP也保持较高水平。尽管心外膜NADH荧光强度表明两组在10分钟低氧灌注期间有氧能量产生的抑制程度相同，但别嘌呤醇治疗组中大量产生乳酸，因此能量通过糖酵解产生增加。这些观察结果表明，别嘌呤醇可预防缺氧-复氧导致的心肌损伤。在低氧灌注期，通过糖酵解维持并改善能量产生，自由基生成减少，脂质过氧化受到抑制。
