Weisel J W, Litvinov R I
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USA.
Cardiovasc Hematol Agents Med Chem. 2008 Jul;6(3):161-80. doi: 10.2174/187152508784871963.
The effectiveness of fibrinolysis results from the combination of regulated enzymatic activity and the physical properties of the fibrin scaffold. Physiologically, clots or thrombi are dissolved from within via internal lysis. In contrast, with therapeutic thrombolysis, lytic agents are introduced at one surface and lysis proceeds across the thrombus. In the latter case, there are complex changes that take place at the lysis front in a narrow zone. However, at the microscopic level the mechanisms for either general type of fibrinolysis appear to be similar. Fibrinolysis proceeds by fibers being transected laterally, rather than digestion of fibers by surface erosion from the outside. A molecular model to account for these observations together with what is known from the biochemical characterization of fibrinolysis involves the movement of plasmin laterally across fibers, binding to sites created by its own proteolytic activity. Fibrin clots can have a great diversity of structural, biological, physical, and chemical properties depending on the conditions of formation, and the rate and nature of fibrinolysis is related to these properties. In general, the rate of lysis appears to be faster for clots made up of thicker fibers than for clots made up of thinner fibers, but the lysis rate is not simply a function of fiber diameter and also depends on other physical properties of the clot. Platelet aggregation and clot retraction have a dramatic effect on the structure of fibrin and hence on fibrinolysis.
纤维蛋白溶解的有效性源于酶活性的调节与纤维蛋白支架物理特性的结合。在生理状态下，凝块或血栓通过内部溶解从内部被溶解。相比之下，在治疗性溶栓过程中，溶栓剂从一个表面引入，溶解过程穿过血栓。在后一种情况下，在狭窄区域的溶解前沿会发生复杂的变化。然而，在微观层面，这两种纤维蛋白溶解类型的机制似乎是相似的。纤维蛋白溶解是通过纤维被横向切断来进行的，而不是通过外部表面侵蚀来消化纤维。一个能够解释这些观察结果以及纤维蛋白溶解生化特征的分子模型涉及纤溶酶在纤维上横向移动，并与由其自身蛋白水解活性产生的位点结合。根据形成条件的不同，纤维蛋白凝块在结构、生物学、物理和化学性质方面可能有很大差异，并且纤维蛋白溶解的速率和性质与这些性质相关。一般来说，由较粗纤维组成的凝块的溶解速率似乎比较细纤维组成的凝块更快，但溶解速率不仅仅是纤维直径的函数，还取决于凝块的其他物理性质。血小板聚集和凝块回缩对纤维蛋白的结构有显著影响，因此对纤维蛋白溶解也有显著影响。
