Neutrophil elastase inhibitor, sivelestat sodium hydrate prevents ischemia-reperfusion injury in the rat bladder
Neutrophil elastase inhibitor, sivelestat sodium hydrate prevents ischemia-reperfusion injury in the rat bladder
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DOI：
10.1007/s11010-007-9698-9
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发表时间：
2008-04-01
影响因子：
4.3
通讯作者：
Saito, Motoaki
中科院分区：
文献类型：
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作者：
Kono, Tomoharu;Okada, Shin-ichi;Saito, Motoaki
在本研究中，我们评估中性粒细胞弹性蛋白酶抑制剂西维来司钠对大鼠膀胱缺血再灌注损伤的影响。用小夹夹闭大鼠腹主动脉，造成膀胱缺血再灌注损伤。将8周龄雄性Sprague道利大鼠分为4组：假手术对照组、30 min缺血-60 min再灌注（IR）大鼠和用15或60 mg/kg西维来司钠水合物处理的IR大鼠。在诱导缺血前60分钟，腹膜内给予西维来司钠水合物。分别用激光多普勒血流仪和NO选择性电极实时监测血流量和一氧化氮（NO）释放。测定膀胱组织中NO2-NO3和丙二醛（MDA）含量。夹闭腹主动脉，血流量迅速减少，NO释放逐渐增加。取出血管夹后，血流量迅速增加，NO释放逐渐恢复到基础水平。西维来司他钠水合物以剂量依赖性方式抑制这些血流和NO释放的运动。IR诱导的大鼠膀胱组织中NO2-NO3和MDA含量均升高，高剂量西维来司钠治疗后，NO2-NO3和MDA含量明显降低。西维来司钠能抑制IR引起的大鼠膀胱组织中NO2-NO3和MDA含量的升高，对IR损伤有潜在的保护作用。
In the present study, we evaluated the effect of neutrophil elastase inhibitor, sivelestat sodium hydrate on ischemia-reperfusion injury in the rat bladder. Rat abdominal aorta was clamping with a small clip to induce ischemia-reperfusion injury in the bladder. Eight-week-old male Sprague Dawley rats were divided into four groups; sham-operated control rats, 30 min ischemia-60 min reperfusion (IR) rats, and IR rats treated with 15 or 60 mg/kg of sivelestat sodium hydrate. Sixty minutes prior to induction of ischemia, sivelestat sodium hydrate was administrated intraperitoneally. Real-time monitoring of blood flow and nitric oxide (NO) release were measured simultaneously with a laser Doppler flowmeter and an NO-selective electrode, respectively. The NO2-NO3 and malonaldehyde (MDA) concentrations were measured in the experimental urinary bladders. Clamping of the abdominal aorta, blood flow was rapidly decreased and NO release was gradually increased. After removing the clip, blood flow was rapidly increased and NO release was gradually returned to the basal level. These movements of blood flow and NO release were inhibited by treatment with sivelestat sodium hydrate in a dose-dependent manner. Both NO2-NO3 and MDA concentrations in the bladder were increased by induction of IR, and NO2-NO3 and MDA concentrations were decreased by treatment with high dose of sivelestat sodium hydrate significantly. Our data indicated that sivelestat sodium hydrate could inhibit increasing NO2-NO3 and MDA concentrations by IR, and it has potentiality protective effects on IR injury in the rat urinary bladder.