轉載自 吳悅宜(碩士論文)-胞漿素原活化對內皮細胞及血小板之間交互作用的影響

胞漿素原活化因子（簡稱t-PA）治療急性心肌塞及其他血管栓塞的疾病可以有效及快速地將血栓溶解。其中約百分之三十的病人易再度栓塞。 正常情況下，血管內壁之單層內皮細胞之完整對於維持血管抗凝性及阻止循環細胞（如．血小板）與內皮細胞下基質接觸是很重要的。我們過去的研究結果顯示，經 靜脈投與大白鼠t-PA或t-PA處理過之人類全血，會使得血小板黏著增強。為探討胞漿素原活化作用對於內皮細胞與血小板之間交互作用的影響，我們以人類 臍帶靜脈內皮細胞作為模擬血管界面的實驗材料，然後依序給予胞漿素原及t-PA模擬溶血栓治療。以扇形平行流體室偵測血小板黏著至經胞漿素原活處理之內皮 細胞表面情形。並利用掃描式電子顯微鏡觀察血小板黏著至內皮細胞表面之形態。研究的結果顯示(一)在線性之流體切應力下，內皮細胞受胞漿素原活化的作用 後，血小板更易黏著其上。此現象會隨時間和濃度之增加而增加；(二)胞漿素之抑制劑（例如EACA及aprotinin）可以抑制胞漿素原活化造成血小板 黏著在內皮細胞上的數目增加及活化現象；(三)胞漿素原活化造成內皮細胞抗助凝特性改變，使得血小板黏著其上，形態更為活化。因此，胞漿素原活化對於內皮 細胞及血小板之間交互作用的影響，是使內皮細胞傾向助凝狀態，造成血小板黏著數目增加且更活化。這些結果也許可以解釋臨床上投與t-PA造成再栓塞的部分 原因。

Fibrinolytic therapy using tissue-type plasminjogen activator (t-PA) is effective in treating acute vascular occlusive diseases. However, for unknown reasons, reocclusion is frequently a major problem. In normal condition, endothelial monolayer integrity is required for controlled vascular antithrombogenesis and to preclude exposure of subendothelial cell matrix to circulating cells, especially platelets. Previous studies from our laboratory showed that platelet adhesion was enhanced either by t-PA administration to the rat in vivo, or by t-PA addition to the anticoagulated human blood in vitro. To investigate whether the endothelium-platelet interactions may be altered by plasminogen activation, cultured human umbilical vein endothelial cells (HUVECs) was treated with t-PA in the presence of plasminogen to mimic the thrombolytic. Platelet adhesion to t-PA treated endothelial cells (ECs) was measured by using a tapered flow chamber that has a linear variation of shear stress across its flow channel. Finally, the morphology of platelets adhered to t-PA treated ECs was observed under a scanning electron microscope. Our results demonstrated that 1) platelets could adhere to the t-PA treated EC monolayer easily, and it was time-dependent and dose-dependent; 2) these phenomena could be abolished by the treatment of plasmin inhibitors. sucin as -amino caproic acld (EACA) and aprotirin; 3) the morphological studies indicated that platelets adhered to t-PA treated ECs were more activated than the control. Therefore, we conclude that t-PA induced plasminogen activation on EC monolayer makes ECs less resistant to platelet adhesion.