Klein-Soyer C, Cazenave J P, Herbert J M, Maffrand J P
INSERM U.311, Centre Régional de Transfusion Sanguine, Strasbourg, France.
J Cell Physiol. 1994 Aug;160(2):316-22. doi: 10.1002/jcp.1041600213.
The thienopyridine, ticlopidine, a potent platelet antiaggregating agent and SR 25989, an esterified derivative of ticlopidine, devoid of antiplatelet activity, were tested in an in vitro model of healing of a mechanical wound in confluent endothelium. This model allows exploration of substances involved in wound healing and angiogenesis. These two compounds inhibited both cell proliferation and cell migration during lesion repair in a dose-dependent manner (18-150 microM), SR 25989 being twice as active as ticlopidine. Its effect was not inhibited by acidic or basic fibroblast growth factor or by platelet derived growth factor. In contrast, it exerted a conjugated inhibition with standard heparin and was able to totally reverse the healing increase induced by a mixture of acidic fibroblast growth factor and heparin. The mechanism of action of SR 25989 is not yet elucidated, but it does not seem to involve competition with fibroblast growth factors since these substances were not able to alter their binding to receptors on the endothelial cell surface. SR 25989 therefore appears as a promising new candidate for inhibition of angiogenesis.
噻吩并吡啶类药物噻氯匹定是一种有效的血小板抗聚集剂，而噻氯匹定的酯化衍生物SR 25989则无抗血小板活性。在汇合内皮细胞的机械性伤口愈合体外模型中对这两种药物进行了测试。该模型可用于探究参与伤口愈合和血管生成的物质。这两种化合物在损伤修复过程中均以剂量依赖性方式（18 - 150微摩尔）抑制细胞增殖和细胞迁移，SR 25989的活性是噻氯匹定的两倍。其作用不受酸性或碱性成纤维细胞生长因子或血小板衍生生长因子的抑制。相反，它与标准肝素产生协同抑制作用，并且能够完全逆转由酸性成纤维细胞生长因子和肝素混合物诱导的愈合增强。SR 25989的作用机制尚未阐明，但似乎不涉及与成纤维细胞生长因子的竞争，因为这些物质无法改变它们与内皮细胞表面受体的结合。因此，SR 25989似乎是一种有前景的新型血管生成抑制剂。
