抑制钠/氢交换体可减轻中性粒细胞介导的再灌注损伤。

Inhibition of Na+/H+ exchanger attenuates neutrophil-mediated reperfusion injury.

作者信息

Faes F C, Sawa Y, Ichikawa H, Shimazaki Y, Ohashi T, Fukuda H, Shirakura R, Matsuda H

机构信息

First Department of Surgery, Osaka University Medical School, Japan.

出版信息

Ann Thorac Surg. 1995 Aug;60(2):377-81. doi: 10.1016/0003-4975(95)00370-z.

DOI:10.1016/0003-4975(95)00370-z

PMID:7646099

Abstract

BACKGROUND

The effect of Na+/H+ exchange inhibition in neutrophil-induced reperfusion injury was investigated using a new amiloride analogue, 5-methyl-N-isobutyl amiloride (MIA).

METHODS

Rat neutrophils were separated using Percoll gradient. Luminol chemiluminescence intensity of isolated neutrophils was depressed by MIA in a dose-dependent manner.

RESULTS

The effect of MIA on neutrophil-induced reperfusion injury was evaluated in Langendorff-perfused rat hearts subjected to 30 minutes of normothermic ischemia. Postischemic left ventricular developed pressure recovery was depressed by the reperfusion with neutrophils (60% +/- 7% to 33% +/- 26%) and was reverted by MIA pretreatment (86% +/- 17%, p < 0.05). MIA also improved percent recovery of coronary flow (51% +/- 2% to 70% +/- 13%), reduced creatine kinase (0.28 +/- 0.1 to 0.085 +/- 0.03 IU.L-1.g-1 dry wt), and lactate dehydrogenase leakage (10.6 +/- 3.8 to 5.16 +/- 1.3 IU.L-1.g-1 dry wt) significantly. The incidence of reperfusion-induced ventricular fibrillation also was reduced by MIA.

CONCLUSIONS

The inhibition of Na+/H+ exchange shows a protective effect against neutrophil-induced reperfusion injury possibly by inhibiting the activation of neutrophils.

摘要

背景

使用一种新的氨氯地平类似物5-甲基-N-异丁基氨氯地平（MIA）研究了中性粒细胞诱导的再灌注损伤中Na+/H+交换抑制的作用。

方法

使用Percoll梯度分离大鼠中性粒细胞。MIA以剂量依赖的方式降低了分离的中性粒细胞的鲁米诺化学发光强度。

结果

在接受30分钟常温缺血的Langendorff灌注大鼠心脏中评估了MIA对中性粒细胞诱导的再灌注损伤的作用。中性粒细胞再灌注使缺血后左心室舒张末压恢复降低（从60%±7%降至33%±26%），而MIA预处理可使其恢复（86%±17%，p<0.05）。MIA还显著改善了冠脉血流恢复百分比（从51%±2%提高到70%±13%），降低了肌酸激酶（从0.28±0.1降至0.085±0.03IU·L-1·g-1干重）和乳酸脱氢酶泄漏（从10.6±3.8降至5.16±1.3IU·L-1·g-1干重）。MIA还降低了再灌注诱导的心室颤动的发生率。