Remote Reperfusion lung injury is associated with AMP deaminase 3 activation and attenuated by inosine monophosphate
Remote Reperfusion lung injury is associated with AMP deaminase 3 activation and attenuated by inosine monophosphate
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DOI：
10.1253/circj.71.591
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发表时间：
2007-04-01
影响因子：
3.3
通讯作者：
Hisatome, Ichiro
中科院分区：
文献类型：
--
作者：
Li, Peili;Ogino, Kazuhide;Hisatome, Ichiro
背景：远端再灌注肺损伤发生在血管闭塞和外科手术的患者中。腺苷单磷酸脱氨酶（AMPD）3产生的肌苷单磷酸（IMP）参与了远端再灌注损伤。本研究的目的是确定是否IMP管理衰减的远程再灌注肺损伤在骨骼肌缺血-再灌注model.Methods和结果远程再灌注肺损伤创建后，再灌注双侧结扎后肢。检测再灌注前后肺组织AMPD活性、髓过氧化物酶（MPO）活性、IMP、AMPD 3 mRNA和肿瘤坏死因子（TNF-α）。此外，还检查了IMP对这些参数的影响。缺血-再灌注后，肺中AMPD 3 mRNA、AMPD活性和IMP产生显著增加，MPO活性、TNF-α水平升高，血氧饱和度（SpO（2））降低。肺组织学检查显示显著的中性粒细胞浸润和积聚。IMP可显著降低MPO活性、TNF-α和中性粒细胞浸润，改善SpO（2）。IMP显著降低肺损伤、MPO活性、TNF-α和增加SpO（2）。这些发现可能导致远程再灌注肺损伤的新的治疗策略的发展。
Background Remote reperfusion lung injury occurs in patients with vascular occlusion and surgical procedures. Inosine monophosphate (IMP) produced by adenosine monophosphate deaminase (AMPD) 3 is involved in the remote reperfusion injury. The purpose of the present study was to identify whether IMP administration attenuated the remote reperfusion lung injury in a skeletal muscle ischemia-reperfusion model.Methods and Results A remote reperfusion lung injury was created using reperfusion after the bilateral ligation of the hind-limb. AMPD activity, myeloperoxidase (MPO) activity, IMP, AMPD3 mRNA and tumor necrosis factor (TNF)-alpha in the lungs before and after reperfusion were analyzed. Furthermore, the effects of IMP on these parameters were examined. AMPD3 mRNA, AMPD activity and IMP production in the lungs significantly increased after ischemia-reperfusion with increases in MPO activity, TNF-alpha level and decreased oxygen saturation (SpO(2)). Histological examination of the lungs demonstrated significant neutrophil infiltration and accumulation. IMP administration significantly reduced MPO activity, TNF-alpha and neutrophil infiltration, with ameliorated SpO(2).Conclusions Along with the activation of AMPD3, ischemia-reperfusion-induced lung inflammation is associated with increased MPO activity and TNF-alpha level. IMP significantly decreased the lung injury, MPO activity, TNF-alpha and increased SpO(2). These findings may lead to the development of a new therapeutic strategy for remote reperfusion lung injury.