Huang L Q, Whitworth J A, Chesterman C N
Department of Medicine, St George Hospital, NSW, Australia.
Blood Coagul Fibrinolysis. 1995 Jul;6(5):438-45. doi: 10.1097/00001721-199507000-00011.
Glucocorticoids reduce prostaglandin synthesis in cultured vascular endothelium, but their effects on other haemostatic functions are unclear. We examined the effects of dexamethasone and cyclosporin A (CSA) on cultured human umbilical vein endothelial cells (HUVEC). One, 10 and 50 micrograms/ml CSA and 1 microgram/ml dexamethasone (Dx) were added to the culture medium for 3 h, 3 days and 6 days and compared with HUVEC cultured in medium and serum alone. After assay of accumulated release of tissue type plasminogen activator (t-PA) and endothelin 1 (ET), cells were stimulated with 1 U/ml of human thrombin for 1 h and medium collected for RIA of 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), thrombospondin (TSP), von Willebrand factor (vWf) and ELISA of plasminogen activator inhibitor 1 (PAI-1). CSA at 1 microgram/ml modestly reduced release of prostacyclin (PGI2) but had no reproducible effects on other metabolites. CSA at 10 and 50 micrograms/ml inhibited cell growth and thrombin stimulated release of PGI2 in a time- and dose-dependent manner. Inhibition of other endothelial metabolites was also observed at CSA 10 > micrograms/ml. Dexamethasone 1 microgram/ml reduced both cell number and PGI2 release and increased thrombin stimulated release of vWf, TSP and PAI-1 with increases in t-PA and endothelin 1 in the medium. CSA 1 microgram/ml and dexamethasone 1 microgram/ml together were additive in reducing PGI2 release and increasing PAI-1 secretion. These observations suggest a role for endothelial dysfunction in the hypertensive and thrombotic complications observed in steroid treated patients with CSA potentially contributing to such complications.
糖皮质激素可减少培养的血管内皮细胞中前列腺素的合成，但其对其他止血功能的影响尚不清楚。我们研究了地塞米松和环孢素A（CSA）对培养的人脐静脉内皮细胞（HUVEC）的影响。将1、10和50微克/毫升的CSA以及1微克/毫升的地塞米松（Dx）添加到培养基中3小时、3天和6天，并与仅在培养基和血清中培养的HUVEC进行比较。在测定组织型纤溶酶原激活剂（t-PA）和内皮素1（ET）的累积释放后，用1单位/毫升的人凝血酶刺激细胞1小时，并收集培养基用于放射免疫分析6-酮前列腺素F1α（6-酮PGF1α）、血小板反应蛋白（TSP）、血管性血友病因子（vWf）以及酶联免疫吸附测定纤溶酶原激活剂抑制剂1（PAI-1）。1微克/毫升的CSA适度降低了前列环素（PGI2）的释放，但对其他代谢产物没有可重复的影响。10和50微克/毫升的CSA以时间和剂量依赖的方式抑制细胞生长和凝血酶刺激的PGI2释放。在10微克/毫升以上的CSA时也观察到对其他内皮代谢产物的抑制作用。1微克/毫升的地塞米松减少了细胞数量和PGI2释放，并增加了凝血酶刺激的vWf、TSP和PAI-1的释放，同时培养基中的t-PA和内皮素1增加。1微克/毫升的CSA和1微克/毫升的地塞米松共同作用时，在降低PGI2释放和增加PAI-1分泌方面具有相加作用。这些观察结果表明，内皮功能障碍在接受类固醇治疗的CSA患者中观察到的高血压和血栓形成并发症中起作用，CSA可能促成此类并发症。
