Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemia-reperfusion injury in rats
Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemia-reperfusion injury in rats
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DOI：
10.1097/00000542-200302000-00028
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发表时间：
2003-02-01
期刊：
影响因子：
8.8
通讯作者：
Ushijima, K
中科院分区：
文献类型：
--
作者：
Yano, T;Anraku, S;Ushijima, K
背景：脑缺血再灌注时急性炎症反应可引起神经元损伤。尿胰蛋白酶抑制剂（UTI）是一种丝氨酸蛋白酶抑制剂，通过其抑制活性对肝、肠、肾、心和肺的缺血-再灌注损伤具有细胞保护作用。乌司他丁对短暂性全脑缺血的神经保护作用已被证实。方法：成年雄性Wistar大鼠随机分为以下治疗组：0.9%生理盐水（对照组，n = 9）; 100，000 U/kg UTI（n = 9）;和300，000 U/kg UTI（n = 9）。在右侧大脑中动脉闭塞2 h和随后的再灌注前10 min进行静脉给药。再灌注后96小时，评估运动神经功能缺损和脑梗死面积。结果：UTI 30万U/kg组脑体积明显小于UTI 10万U/kg组和生理盐水对照组（P <0.05），UTI 30万U/kg组脑体积明显小于UTI 10万U/kg组和生理盐水对照组（P < 0.05）。300，000 U/kg UTI治疗显示出改善神经功能结局的趋势，但未达到统计学显著性（P = 0.0693）。与生理盐水对照组相比，在用300，000 U/kg UTI治疗的缺血半球中观察到中性粒细胞浸润的显著减少（P < 0.05）。与生理盐水对照组和10万U/kg UTI组相比，30万U/kg UTI组缺血侧脑组织硝基酪氨酸沉积明显减少（P <0. 05）。静脉预处理300，000 U/kg UTI可减轻大鼠脑局灶性缺血再灌注损伤，可能为脑缺血治疗开辟新的治疗途径。
Background: Acute inflammatory reactions cause neuronal damage in cerebral ischemia-reperfusion. Urinary trypsin Inhibitor (UTI), a serine protease inhibitor, is cytoprotective against ischemia-reperfusion injury in the liver, intestine, kidney, heart, and lung through its antiinflammatory activity. Neuroprotective action of UTI on transient global cerebral ischemia has been documented. This is the first study to determine whether UTI is neuroprotective against transient focal cerebral ischemia.Methods: Adult male Wistar rats were randomly assigned to the following treatment groups: 0.9% saline (control, n = 9); 100,000 U/kg UTI (n = 9); and 300,000 U/kg UTI (n = 9). Treatments were performed intravenously 10 min before right middle cerebral artery occlusion for 2 h and subsequent reperfusion. Ninety-six hours after the onset of reperfusion, the motor neurologic deficit and the cerebral infarct size were evaluated. Furthermore, immunohistochemical staining for myeloperoxidase and nitrotyrosine to count infiltrating neutrophils and nitrated cells, respectively, was performed on the brain sections.Results: Infarct volume in the 300,000 U/kg UTI group was smaller than in the 100,000 U/kg UTI and saline control groups (P < 0.05). Treatment with 300,000 U/kg UTI showed a trend to improve neurologic outcome but did not reach statistical significance (P = 0.0693). The significant decrease in neutrophil infiltration was observed in the ischemic hemisphere treated with 300,000 U/kg UTI compared with saline control (P < 0.05). Nitrotyrosine deposition in the ischemic hemisphere was significantly reduced in the 300,000 U/kg UTI group compared with saline control and 100,000 U/kg UTI groups (P < 0.05).Conclusions. Intravenous pretreatment with 300,000 U/kg UTI reduces focal ischemia-reperfusion injury in the rat brain, potentially opening a novel therapeutic avenue for the treatment of cerebral ischemia.