Department of Physiology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama 589-8511, Japan.
Thromb Res. 2010 May;125(5):e214-21. doi: 10.1016/j.thromres.2009.12.009. Epub 2010 Jan 10.
Although the involvement of plasminogen in liver repair has been reported, its roles are still poorly understood. Here, we investigated the role of plasminogen in accumulations of macrophages and neutrophils after liver injury in mice with gene deficient of plasminogen (Plg(-/-)) or its wild type (Plg(+/+)).
Mice received traumatic liver injury caused by stabbing on the lobe or hepatic ischemia-reperfusion, and the damaged sites were histologically analyzed.
After the traumatic liver injury, both the stab wound and the damaged tissue were decreased until day 7 in the Plg(+/+) mice. In contrast, both the stab wound and the damaged tissue were still remained until day 7 in the Plg(-/-) mice. On day 4 after traumatic liver injury, macrophages were abundant at the surrounding area of the damaged site in the Plg(+/+) mice. However, the macrophage accumulation was impaired in the Plg(-/-) mice. After hepatic ischemia-reperfusion injury, macrophage accumulation and decrease in the damaged tissue were also observed in the Plg(+/+) mice until day 7. In contrast, these responses were also impaired in the Plg(-/-) mice. Furthermore, neutrophil accumulation at the surrounding area of the damaged site was also impaired in the Plg(-/-) mice on day 4 after both liver traumatic liver injury and hepatic ischemia-reperfusion injury.
Our data indicate that plasminogen plays a crucial role in macrophage accumulation together with the neutrophil accumulation after liver injury in both models, which may be essential for triggering the subsequent healing responses including decrease in the damaged tissue.
尽管已有研究报道纤溶酶原参与肝脏修复，但对其作用仍知之甚少。本研究旨在探讨纤溶酶原基因敲除（Plg(-/-)）或野生型（Plg(+/+)）小鼠肝脏损伤后巨噬细胞和中性粒细胞积聚中纤溶酶原的作用。
通过刺伤肝脏叶或肝缺血再灌注造成小鼠肝脏损伤，对损伤部位进行组织学分析。
在 Plg(+/+)小鼠中，刺伤伤和损伤组织在第 7 天前逐渐减少，但在 Plg(-/-)小鼠中，这两种情况一直持续到第 7 天。在创伤性肝损伤后第 4 天，Plg(+/+)小鼠损伤部位周围有大量巨噬细胞。然而，在 Plg(-/-)小鼠中，巨噬细胞积聚受损。在肝缺血再灌注损伤后，Plg(+/+)小鼠的巨噬细胞积聚和损伤组织减少在第 7 天前也有观察到。相反，在 Plg(-/-)小鼠中，这些反应也受损。此外，在创伤性肝损伤和肝缺血再灌注损伤后第 4 天，Plg(-/-)小鼠损伤部位周围的中性粒细胞积聚也受损。
我们的数据表明，纤溶酶原在两种模型的肝损伤后巨噬细胞和中性粒细胞积聚中发挥关键作用，这对于触发包括损伤组织减少在内的后续愈合反应可能是必要的。
