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Mini-Review Article

识别纤溶酶原激活物抑制剂1作为纤溶的主要调节剂

卷 20, 期 16, 2019

页: [1695 - 1701] 页: 7

弟呕挨: 10.2174/1389450120666190715102510

摘要

纤溶系统由纤溶酶原激活率和纤维蛋白降解率之间的平衡组成，两者均受时空机制的调控。纤溶系统的三种不同的抑制剂分别调节这两个步骤，分别是纤溶酶原激活物抑制剂1型（PAI-1），α2-抗纤溶酶和凝血酶可激活的纤溶酶抑制剂（TAFI）。在这篇综述中，我们重点研究PAI-1控制总纤溶活性的机制，以提供其在许多止血性疾病（包括创伤后纤溶性关闭）中的重要作用。 PAI-1是丝氨酸蛋白酶抑制剂（SERPIN）超家族的成员，并通过与PAs形成复合物来抑制纤溶酶原激活剂（PAs）的蛋白酶活性，从而调节纤维蛋白溶解。脉管系统中的主要PA是组织型PA（tPA），它是从血管内皮细胞（VEC）分泌的一种活性酶，并保留在VEC的表面上。存在于血浆中tPA摩尔过量的PAI-1通过形成tPA-PAI-1复合物来调节血浆和VEC表面的游离活性tPA量。因此，PAI-1的高血浆水平直接与纤溶作用减弱和血栓形成的风险增加直接相关。由于血浆PAI-1水平在包括感染和炎症在内的各种病理条件下高度升高，因此血浆和VEC上的纤溶潜力很容易被抑制，从而导致纤溶关闭。人类的先天性PAI-1缺乏反过来导致威胁生命的出血。这些考虑因素支持以下论点：PAI-1是纤维蛋白溶解初始步骤的主要调节剂，并控制总的纤维蛋白溶解活性。

关键词: 纤溶酶原激活物抑制剂1型（PAI-1），组织型纤溶酶原激活物（tPA），纤溶，纤溶潜力，创伤，纤溶关闭。

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