The regulation of liver regeneration by the plasmin/α2-antiplasmin system
The regulation of liver regeneration by the plasmin/α2-antiplasmin system
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DOI：
10.1016/j.jhep.2003.09.016
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发表时间：
2004-01-01
影响因子：
25.7
通讯作者：
Matsuo, O
中科院分区：
文献类型：
--
作者：
Okada, K;Ueshima, S;Matsuo, O
背景/目的：肝损伤后的再生受多种生长因子的释放和激活调节。研究纤溶酶/α(2)-抗纤溶酶(α(2)-AP)系统在肝再生中的作用。方法：将CCl4注入纤溶因子缺陷(-/-)小鼠：α(2)-AP纤溶酶原(PLG)-/-、PLG-/-、α(2)-AP-/-，以及野生型(WT)小鼠。结果：基因缺陷小鼠和WT小鼠注射CCl4 2天后，肝组织均出现相同程度的坏死。WT组小鼠肝脏在7天后恢复正常，α(2)-AP-/-小鼠在5天后恢复正常。相比之下，PLG-/-和PLG-/-α(2)-AP-/-小鼠的肝脏一直处于受损状态，直到肝损伤后14天。WT小鼠注射抗α(2)-AP抗体可促进肝损伤后的再生，而α(2)-AP-/-小鼠注射氨甲环酸的量减少。结论：纤溶酶/α(2)-AP系统通过清除肝损伤区域在肝修复中发挥重要作用。(C)2003年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: The regeneration after liver injury is regulated by the release and activation of several growth factors. The role of the plasmin/alpha(2)-antiplasmin (alpha(2)-AP) system in liver regeneration was investigated.Methods: CCl4 was injected intraperitoneally into the mice deficient (-/-) in fibrinolytic factors: alpha(2)-AP plasminogen (Plg) -/-, and Plg -/-.alpha(2)-AP -/-, and wild-type (WT) mice. The liver tissue was examined for its microscopic appearance, fibrinolytic activity, and fibronectin levels.Results: In the gene deficient and WT mice, the livers exhibited the same extent of necrosis 2 days after the CCl4 injection. The livers of the WT mice normalized after 7 days, and the alpha(2)-AP -/- mice normalized after 5 days. In contrast, the livers of the Plg -/- and Plg -/-.alpha(2)-AP -/- mice remained in the damaged state until 14 days after the liver injury. The injection of anti-alpha(2)-AP antibody in the WT mice improved the regeneration after the liver injury, and the injection of tranexamic acid in the alpha(2)-AP -/- mice reduced.Conclusions: These results suggest that the plasmin/alpha(2)-AP system played an important role in hepatic repair via clearance from the injury area. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.