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Protective Effects of Urinary Trypsin Inhibitor(UTI) on Hepatic Microvasculature in Hypotensive Brain-Dead Rats

尿胰蛋白酶抑制剂（UTI）对低血压脑死亡大鼠肝微血管的保护作用

基本信息

批准号：
12671172
负责人：
SATO Koshi
金额：
$ 2.11万
依托单位：
KITASATO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671172/
关键词：
brain death liver hepatic tissue flow protease inhibitor

项目摘要

Background/aims : We examined the protective effects of a protease inhibitor, urinary trypsin inhibitor (UTI), on brain dead livers associated with systemic hemodynamic instability. Methods : Brain death was induced by inflating a balloon catheter placed in the epidural space in rats followed by intravenous administration of UTI for 6 hours. The hemodynamic, functional and morphological changes in the liver were examined. Results : The induction of brain death resulted in a significant decrease in both mean arterial pressure (MAP) and hepatic tissue flow (HTF), and an increase in serum AST and cytokines such as tumor necrosis factor (TNF)-alpha and cytokines-induced neutrophil chemoattractant (CINC). An increase in the number of sequestered neutrophils and enhanced expressions of intercellular adhesion molecules (ICAM)-1 and CINC were also noted in the liver. The treatment with UTI significantly restored HTF to basal level without affecting MAP, and decreased the number of sequestered neutrophils in the hepatic sinusoids, suppressed the expression of ICAM-1 and CINC in the sinusoids, inhibited the production of serum TNF-alpha and CINC, and inactivated Kupffer cells. Conclusions : Intravenous administration of UTI is likely to ease unfavorable effects on the hepatic microvasculature evoked by brain death.

背景/目标：我们研究了一种蛋白酶抑制剂，尿胰蛋白酶抑制剂（UTI），对与全身血流动力学不稳定相关的脑死亡肝脏的保护作用。研究方法：脑死亡是通过膨胀放置在大鼠硬膜外腔中的球囊导管，然后静脉内施用UTI 6小时来诱导的。观察肝脏血流动力学、功能及形态学变化。结果如下：诱导脑死亡导致平均动脉压（MAP）和肝组织流量（HTF）显著降低，血清AST和细胞因子（如肿瘤坏死因子（TNF）-α和细胞因子诱导的中性粒细胞趋化因子（CINC））升高。在肝脏中还观察到隔离的中性粒细胞数量增加和细胞间粘附分子（ICAM）-1和CINC表达增强。UTI治疗显著恢复HTF至基础水平而不影响MAP，减少肝窦中隔离的中性粒细胞数量，抑制肝窦中ICAM-1和CINC的表达，抑制血清TNF-α和CINC的产生，并灭活枯否细胞。结论：静脉注射UTI可能减轻脑死亡引起的对肝脏微血管的不利影响。