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ROLES OF PLASMINOGEN ACTIVATORS UPON BRAIN INJURY

纤溶酶原激活剂对脑损伤的作用

基本信息

批准号：
10671332
负责人：
KATAOKA Kazuo
金额：
$ 1.92万
依托单位：
KINKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671332/
关键词：
Plasminogen activator Brain injury Angiogenesis Brain edema 脳浮腫ミクログリア神経外傷 uPA tPA

项目摘要

Urokinase type plasminogen activator (uPA) involves tissue fibrinolysis that is related to the healing process, development, and tumor invasion. Plasminogen inhibitor-1 (PAI-1) inhibits the protelytic activity of uPA and may enhance the brain vasculature after brain injury. We studied brain edema and changes in the vasculature after a brain stab wound in uPA-deficient, uPA receptor-deficient, and PAI-1-deficient mice, and control mice. Compared to control mice, the extravasation of immunoglobulin was significantly greater in PAI 1 deficient mice at 3 days after the lesion was placed, less pronounced in uPA-deficient mice and similar to the controls in uPA receptor-deficient mice. Von Willebrand factor-positive vascular structures increased in number 8 days after lesioning in PAI-1 deficient mice. Furthermore, irregular and proliferative collagen Type IV-positive microvasculatures were observed in all PAI-1-deficient mice and in 20% of control mice 8 days after lesion placement. Those findings are indicative of increased angiogenesis. Our study clearly shows that uPA contributes to the development of secondary brain damage due to a breakdown of microvascular extracellular matrix protein, and that uPA plays a role without binding to its receptor in the acute stage. PAI-1 inhibits traumatic brain edema. On the other hand, plasminogen activator facilitates angiogenesis necessary for healing after brain injury.

尿激酶型纤溶酶原激活物（uPA）参与组织纤维蛋白溶解，其与愈合过程、发展和肿瘤侵袭有关。纤溶酶原抑制剂-1（派-1）可抑制uPA的蛋白水解活性，并可增强脑损伤后的脑血管。我们研究了uPA缺陷型、uPA受体缺陷型和派-1缺陷型小鼠以及对照小鼠脑刺伤后的脑水肿和血管变化。与对照组小鼠相比，派1缺陷型小鼠的免疫球蛋白外渗在损伤后3天显著更大，uPA缺陷型小鼠不太明显，而uPA受体缺陷型小鼠与对照组相似。血管性血友病因子阳性血管结构的数量增加8天后，在派-1缺陷型小鼠病变。此外，在所有派-1缺陷小鼠和20%的对照小鼠中观察到病变放置后8天的不规则和增殖的IV型胶原阳性微血管。这些发现表明血管生成增加。我们的研究清楚地表明，由于微血管细胞外基质蛋白的分解，uPA有助于继发性脑损伤的发展，并且uPA在急性期发挥作用而不与其受体结合。派-1抑制创伤性脑水肿。另一方面，纤溶酶原激活剂促进脑损伤后愈合所必需的血管生成。