Prevention of leukocyte activation by the neutrophil elastase inhibitor, sivelestat, in the hepatic microcirculation after ischemia-reperfusion.
Prevention of leukocyte activation by the neutrophil elastase inhibitor, sivelestat, in the hepatic microcirculation after ischemia-reperfusion.
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DOI：
10.1016/j.jss.2008.07.025
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发表时间：
2009-08
期刊：
影响因子：
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通讯作者：
Y. Nakano;T. Kondo;R. Matsuo;S. Murata;K. Fukunaga;N. Ohkohchi
中科院分区：
文献类型：
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作者：
Y. Nakano;T. Kondo;R. Matsuo;S. Murata;K. Fukunaga;N. Ohkohchi
肝脏缺血再灌注损伤（I/R）是肝脏外科最严重的并发症之一。然而，临床上还没有有效的治疗方法。中性粒细胞弹性蛋白酶抑制剂（NEI）已被临床用于治疗急性肺损伤，但NEI对肝I/R后肝微循环中白细胞动力学的影响尚不清楚。本研究的目的是利用活体显微镜（IVM）来评价NEI对肝I/R后肝微循环中白细胞动力学的影响。方法雄性SD大鼠诱导肝缺血。缺血前给予西维来司他、特异性NEI或生理盐水（NS）持续静脉输注。再灌注后120分钟，观察肝微循环中粘附白细胞的数量和窦灌注的障碍。结果西维来司他能显著降低白细胞粘附数，改善肝灌注障碍。此外，西维来司他明显改善肝损伤的组织学检查结果和肝酶，并防止MDA的增加。CONCLUSIONSAgmentation西维来司他缺血前有效地抑制白细胞和脂质过氧化物的激活，从而防止肝I/R损伤。
BACKGROUNDLiver ischemia-reperfusion (I/R) injury is one of the most serious complications of hepatic surgery. However, no effective treatment is yet clinically available. Although neutrophil elastase inhibitor (NEI) has been used clinically in acute lung injury, the effect of NEI on leukocyte dynamics in the liver microcirculation after hepatic I/R remained unclear. The purpose of this study was to use intravital microscopy (IVM) to evaluate the effect of NEI on leukocyte dynamics in the liver microcirculation after hepatic I/R.METHODSHepatic ischemia was induced in male Sprague-Dawley (SD) rats. Sivelestat, a specific NEI, or normal saline (NS) was given as a continuous intravenous infusion before ischemia. The number of adherent leukocytes and the disturbances of sinusoidal perfusion in hepatic microcirculation were observed up to 120 minutes after reperfusion. Samples of liver tissue and blood were taken for histological examination and measurement of liver enzymes and tissue malondialdehyde (MDA).RESULTSCompared with NS, sivelestat significantly decreased the number of adherent leukocytes and prevented perfusion disturbance. In addition, sivelestat obviously improved liver injury as assessed by histological findings and liver enzymes, and prevented the increase of MDA.CONCLUSIONSAdministration of sivelestat before ischemia effectively suppressed the activation of leukocytes and lipid peroxide, and it consequently prevented hepatic I/R injury.