Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Ube, Yamaguchi, Japan.
Inflamm Res. 2010 Aug;59(8):597-606. doi: 10.1007/s00011-010-0166-8. Epub 2010 Feb 11.
The protective effects of ulinastatin, a human urinary trypsin inhibitor (UTI), against superoxide radical (O(2)(-*)) generation, systemic inflammation, lipid peroxidation, and endothelial injury were investigated in endotoxemic rats.
Twenty-one Wistar rats were allocated to a control group, a UTI group, and a sham group. A bolus of lipopolysaccharide (LPS; 3 microg/g) was administered intravenously to the control group, a bolus of LPS and UTI (5 U/g) to the UTI group, and a bolus of saline to the sham group.
The O(2)(-) generated was measured as the current in the right atrium using an electrochemical O(2)(-) sensor. Plasma nitrite, high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, malondialdehyde, and soluble intercellular adhesion molecule-1 (sICAM-1) were measured 360 min after LPS administration.
The O(2)(-*) current increased in the control group and was significantly attenuated in the UTI group after 55 min (P < 0.05 at 55-60 min, P < 0.01 at 65-360 min). Plasma nitrite, HMGB1, TNF-alpha, IL-6, malondialdehyde, and sICAM-1 were attenuated in the UTI group.
UTI suppressed excessive O(2)(-*) generation, systemic inflammation, lipid peroxidation, and endothelial injury in endotoxemic rats.
本研究旨在探讨人尿胰蛋白酶抑制剂（UTI）对脓毒症大鼠超氧阴离子（O2（-*））生成、全身炎症、脂质过氧化和内皮损伤的保护作用。
21 只 Wistar 大鼠分为对照组、UTI 组和假手术组。对照组静脉注射脂多糖（LPS；3μg/g），UTI 组注射 LPS 和 UTI（5U/g），假手术组注射生理盐水。
使用电化学 O2（-）传感器测量右心房电流来测量生成的 O2（-）。LPS 给药后 360 分钟测量血浆亚硝酸盐、高迁移率族蛋白框 1（HMGB1）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、丙二醛和可溶性细胞间黏附分子-1（sICAM-1）。
对照组 O2（-*）电流增加，UTI 组在 55 分钟后明显减弱（55-60 分钟时 P < 0.05，65-360 分钟时 P < 0.01）。UTI 组血浆亚硝酸盐、HMGB1、TNF-α、IL-6、丙二醛和 sICAM-1 水平降低。
UTI 抑制了脓毒症大鼠过度的 O2（-*）生成、全身炎症、脂质过氧化和内皮损伤。
