Na+/H+ Exchange Inhibitor SM‐20220 Attenuates Leukocyte Adhesion Induced By Ischemia‐Reperfusion
Na+/H+ Exchange Inhibitor SM‐20220 Attenuates Leukocyte Adhesion Induced By Ischemia‐Reperfusion
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DOI：
10.1097/00005344-200106000-00004
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发表时间：
2001-06
影响因子：
3
通讯作者：
N. Horikawa;Y. Kuribayashi;K. Matsui;N. Kawamura;N. Ohashi
中科院分区：
文献类型：
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作者：
N. Horikawa;Y. Kuribayashi;K. Matsui;N. Kawamura;N. Ohashi
&NA;白细胞在缺血再灌注诱导的组织损伤中起关键作用。已经提出，阻断Na+/H+交换器改善缺血性损伤，例如中风。在这项研究中，我们研究了Na+/H+交换抑制剂SM-20220（N-[氨基亚氨基甲基]-1-甲基-1-吲哚-2-甲酰胺甲磺酸盐）对缺血-再灌注期间白细胞-内皮细胞相互作用的影响。SM-20220（0.3-1.0 mg/kg i.v.）在缺血后给药显著减弱了由短暂的上级肠系膜动脉闭塞引起的肠系膜毛细血管后微静脉中的白细胞粘附。在再灌注后60 min，溶剂或SM-20220（0.3 mg/kg）处理组的粘附白细胞数量分别为15.1 ± 2.9个细胞/100 m2/3 min和3.0 ± 0.7个细胞/100 m2/3 min（p < 0.01）。在短暂性大脑中动脉闭塞模型中，与溶剂组相比，从闭塞开始后1小时开始静脉输注SM-20220（0.4 mg/kg/h）1小时，可显著降低梗死面积和脑髓过氧化物酶活性的增加（分别为p < 0.01和p < 0.05）。总之，这是第一个证据表明，缺血-再灌注诱导的白细胞粘附到内皮上，通过抑制体内Na+/H+交换活性而减弱。我们的研究结果表明，Na+/H+交换抑制剂可以部分通过减弱白细胞-内皮细胞相互作用来预防缺血再灌注损伤，如中风。
&NA; Leukocytes play a key role in ischemia‐reperfusion‐induced tissue injuries. It has been suggested that blocking the Na+/H+ exchanger improves ischemic injuries such as stroke. In this study, we investigated the effect of the Na+/H+ exchanger inhibitor SM‐20220 (N‐[aminoiminomethyl]‐1‐methyl‐1Hindole‐2‐carboxamide methanesulfonate) on leukocyte‐endothelial cell interactions during ischemia‐reperfusion. SM‐20220 (0.3–1.0 mg/kg i.v.) given after ischemia significantly attenuated the leukocyte adhesion in the mesenteric postcapillary venules that was induced by transient superior mesenteric artery occlusion. At 60 min after reperfusion, the numbers of adherent leukocytes in groups treated with vehicle or SM‐20220 (0.3 mg/kg) were 15.1 ± 2.9 cells/100 m/3 min and 3.0 ± 0.7 cells/100 m/3 min (p < 0.01), respectively. In a transient middle cerebral artery occlusion model, i.v. infusion of SM‐20220 (0.4 mg/kg per hour) for 1 h, beginning 1 h after the start of occlusion, significantly reduced both the infarct size and the increase in brain myeloperoxidase activity, compared with the vehicle group (p < 0.01 and p < 0.05, respectively). In summary, this is the first evidence that the leukocyte adhesion to the endothelium that is induced by ischemia‐reperfusion is attenuated by the inhibition of Na+/H+ exchanger activity in vivo. Our results suggest that Na+/H+ exchanger inhibitors may prevent ischemia‐reperfusion injuries such as stroke partly through the attenuation of leukocyte‐endothelial cell interactions.