Voss B L, Hamilton K K, Samara E N, McKee P A
Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Transplantation. 1988 Apr;45(4):793-6. doi: 10.1097/00007890-198804000-00025.
The effects of cyclosporine (CsA) on prostacyclin (PGI2) release by cultured human umbilical vein endothelial cells were investigated. PGI2 production was measured by radioimmunoassay of its stable metabolite 6-Keto-PGF1 alpha. CsA induced a time and concentration-dependent reduction in unstimulated (basal) and Ca++ ionophore (A23187)-stimulated release of PGI2. A 16-hr incubation with CsA reduced A23187 PGI2 release by 64% (P less than 0.05); CsA at concentrations of 1.0, 10.0, and 100.0 micrograms/ml reduced A23187 PGI2 release by 67%, 80%, and 90%, respectively (P less than 0.05). This suppression was reversed within 24 hr after withdrawal of CsA. Arachidonic acid-stimulated PGI2 release was also decreased in CsA-treated cells, indicating an inhibitory effect distal to phospholipase A2. 3H-deoxyglucose release, an indicator of cell injury, was not increased by CsA, thus excluding nonspecific cell damage as a mechanism of the observed suppressive effect. This inhibition of PGI2 release from endothelial cells by CsA may explain the increased renal vascular resistance and renal microvascular thrombosis seen on occasion with CsA administration.
研究了环孢素（CsA）对培养的人脐静脉内皮细胞释放前列环素（PGI2）的影响。通过对其稳定代谢产物6-酮-前列腺素F1α进行放射免疫测定来检测PGI2的生成。CsA诱导未刺激（基础）状态和钙离子载体（A23187）刺激状态下的PGI2释放出现时间和浓度依赖性降低。与CsA孵育16小时可使A23187刺激的PGI2释放降低64%（P<0.05）；浓度为1.0、10.0和100.0微克/毫升的CsA分别使A23187刺激的PGI2释放降低67%、80%和90%（P<0.05）。在撤除CsA后24小时内，这种抑制作用可逆转。在经CsA处理的细胞中，花生四烯酸刺激的PGI2释放也减少，这表明在磷脂酶A2作用远端存在抑制效应。作为细胞损伤指标的3H-脱氧葡萄糖释放并未因CsA而增加，因此排除了非特异性细胞损伤作为所观察到的抑制效应机制的可能性。CsA对内皮细胞释放PGI2的这种抑制作用可能解释了使用CsA时偶尔出现的肾血管阻力增加和肾微血管血栓形成现象。
