Kurose I, Miura S, Fukumura D, Tashiro H, Imaeda H, Shiozaki H, Suematsu M, Nagata H, Sekizuka E, Tsuchiya M
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Gut. 1992 Jul;33(7):868-71. doi: 10.1136/gut.33.7.868.
We have examined the hypothesis that the release of tissue type plasminogen activator may play a prominent role in endothelin induced gastric mucosal injury. We determined tissue type plasminogen activator activity in the regional blood sample and the concentration of platelet activating factor in the gastric mucosa after the administration of endothelin-1 in a range of 50-500 pmol/kg into the left gastric artery of male Wistar rats. Endothelin-1 increased the tissue type plasminogen activator release and platelet activating factor formation, and induced subsequent gastric mucosal haemorrhagic change in a dose dependent manner. In addition CV-6209, a selective platelet activating factor blocker, attenuated the activation of regional tissue type plasminogen activator and the development of mucosal damage induced by endothelin-1. The results of this study showed that tissue type plasminogen activator activation may play an important role in the pathogenesis of endothelin induced mucosal injury of rat stomach, and suggest that the platelet activating factor may be involved in the process of regional fibrinolytic activation induced by endothelin-1.
我们研究了组织型纤溶酶原激活物的释放可能在内皮素诱导的胃黏膜损伤中起重要作用这一假说。在雄性Wistar大鼠的胃左动脉内注射50 - 500 pmol/kg的内皮素-1后，我们测定了局部血样中的组织型纤溶酶原激活物活性以及胃黏膜中血小板活化因子的浓度。内皮素-1以剂量依赖的方式增加了组织型纤溶酶原激活物的释放和血小板活化因子的形成，并引发了随后的胃黏膜出血性改变。此外，选择性血小板活化因子阻滞剂CV - 6209减弱了局部组织型纤溶酶原激活物的活化以及内皮素-1诱导的黏膜损伤的发展。本研究结果表明，组织型纤溶酶原激活物的活化可能在大鼠胃内皮素诱导的黏膜损伤发病机制中起重要作用，并提示血小板活化因子可能参与了内皮素-1诱导的局部纤溶激活过程。
