PAI-1 plays an important role in liver failure after excessive hepatectomy in the rat
PAI-1 plays an important role in liver failure after excessive hepatectomy in the rat
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DOI：
10.1016/j.jss.2007.04.041
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发表时间：
2007-11-01
影响因子：
2.2
通讯作者：
Shimada, Hiroshi
中科院分区：
文献类型：
--
作者：
Watanabe, Kazuteru;Togo, Shinji;Shimada, Hiroshi
背景/目标。细胞外基质的有组织的周转在肝再生中很重要，它受纤溶酶原激活系统的调节。本研究旨在探讨纤溶酶原激活物抑制物-1(PAI-1)在大鼠肝大部切除后的作用，以及血管紧张素转换酶(ACE)抑制物是否能有效提高95%肝部分切除(PHX)大鼠的存活率。分别于90%和95%PHX后取肝组织，用逆转录聚合酶链式反应检测肝组织PAL 1mRNA的表达。采用酶联免疫吸附试验检测肝组织PAI-1蛋白和尿激酶型纤溶酶原激活物(UPA)水平。通过存活观察和5-溴-2‘-脱氧尿嘧啶核苷染色细胞动力学分析评价ACE抑制作用。95%PHX组肝组织PAI-1蛋白和PAI-1mRNA表达水平均达到峰值，并维持在最高水平。相比之下，uPA水平相对于90%PHX组下降。此外，在接受ACE抑制的95%PHX大鼠中，肝脏PAI-1蛋白水平降低，存活率提高。我们的实验结果表明，PAI-1通过加速uPA原和纤溶因子的成熟，在过度肝切除后肝功能衰竭的发生中起作用。这些都是治疗过度肝切除术后肝功能衰竭的潜在分子治疗靶点。(C)2007 Elsevier Inc.保留所有权利。
Background/Aims. Well-organized turnover of the extracellular matrix is important in liver regeneration, which is regulated by the plasminogen activating system. The aim of this study was to investigate the role of plasminogen activator inhibitor-1 (PAI-1) after excessive hepatectomy and to ascertain whether angiotensin-converting enzyme (ACE) inhibitors, which are PAI-1 inhibitors as well, successfully improve the survival rate of rats that have undergone 95% partial hepatectomy (PHx).Methods. Using liver tissues sampled after 90% or 95% PHx, the expression of PAL 1 mRNA was evaluated using reverse transcription polymerase chain reaction. Hepatic PAI-1 protein and urokinase-type plasminogen activator (uPA) levels were determined by enzyme-linked immunosorbent assay. Survival study and cytodynamic analysis by 5-bromo-2'-deoxyuridine staining were performed to evaluate the effects of ACE inhibition.Results. The levels of PAI-1 mRNA and hepatic PAI-1 protein in the 95% PHx group peaked and were then maintained. By contrast, the uPA level fell relative to the 90% PHx group. Additionally, the hepatic PAI-1 protein level decreased and the survival rate improved in the 95% PHx rats that had undergone ACE inhibition.Conclusions. Our experimental results suggest that PAI-1 plays a role in the occurrence of liver failure after excessive hepatectomy via accelerated maturation of pro-uPA and fibrinolytic factors. These are potential molecular therapeutic targets for liver failure after excessive hepatectomy. (c) 2007 Elsevier Inc. All rights reserved.