Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
Shanghai Engineering Research Center of Aquatic-Product Processing and Preservation, Shanghai 201306, China.
Mar Drugs. 2022 Jul 30;20(8):495. doi: 10.3390/md20080495.
Fungi fibrinolytic compound 1 (FGFC1) is a rare pyran-isoindolone derivative with fibrinolytic activity. The aim of this study was to further determine the effect of FGFC1 on fibrin clots lysis in vitro. We constructed a fibrinolytic system containing single-chain urokinase-type plasminogen activator (scu-PA) and plasminogen to measure the fibrinolytic activity of FGFC1 using the chromogenic substrate method. After FITC-fibrin was incubated with increasing concentrations of FGFC1, the changes in the fluorescence intensity and D-dimer in the lysate were measured using a fluorescence microplate reader. The fibrin clot structure induced by FGFC1 was observed and analyzed using a scanning electron microscope and laser confocal microscope. We found that the chromogenic reaction rate of the mixture system increased from (15.9 ± 1.51) × 10−3 min−1 in the control group to (29.7 ± 1.25) × 10−3 min−1 for 12.8 μM FGFC1(p < 0.01). FGFC1 also significantly increased the fluorescence intensity and d-dimer concentration in FITC fibrin lysate. Image analysis showed that FGFC1 significantly reduced the fiber density and increased the fiber diameter and the distance between protofibrils. These results show that FGFC1 can effectively promote fibrin lysis in vitro and may represent a novel candidate agent for thrombolytic therapy.
真菌纤维蛋白溶解化合物 1（FGFC1）是一种罕见的吡喃-异吲哚啉衍生物，具有纤维蛋白溶解活性。本研究旨在进一步确定 FGFC1 对体外纤维蛋白凝块溶解的影响。我们构建了一个含有单链尿激酶型纤溶酶原激活剂（scu-PA）和纤溶酶的纤溶系统，使用比色底物法测量 FGFC1 的纤溶活性。用不同浓度的 FGFC1 孵育 FITC-纤维蛋白后，用荧光微孔板读数仪测量裂解液中荧光强度和 D-二聚体的变化。用扫描电子显微镜和激光共聚焦显微镜观察和分析 FGFC1 诱导的纤维蛋白凝块结构。我们发现，在对照组中，混合物系统的比色反应速率从（15.9 ± 1.51）×10−3 min−1增加到 12.8 μM FGFC1 的（29.7 ± 1.25）×10−3 min−1（p < 0.01）。FGFC1 还显著增加了 FITC 纤维蛋白裂解液的荧光强度和 d-二聚体浓度。图像分析表明，FGFC1 显著降低了纤维密度，增加了纤维直径和原纤维之间的距离。这些结果表明，FGFC1 可有效促进体外纤维蛋白溶解，可能代表溶栓治疗的一种新型候选药物。
