Fakir M, Wegrowski J, Bour P, Joundi A, Chanard J, Maquart F X
Néphrologie Transplantation Rénale, CHU, Reims.
Presse Med. 1992 Dec 2;21(41):1951-3.
Interstitial renal fibrosis and gingival hypertrophy are frequent side-effects of cyclosporin A which have been attributed to a dysfunction of extracellular matrix synthesis. Endothelial cells might participate in the matrix accumulation observed. We studied the effects of increasing concentrations of cyclosporin A on protein synthesis by human umbilical vein endothelial cells. Collagen synthesis decreased significantly to 800 ng/ml in both medium and cell layer. The percentage of hydroxylation of its proline residues decreased significantly as from 400 ng/ml. The main proteins, analysed by SDS-PAGE, were thrombospondin, fibronectin and the alpha 1 and alpha 2 chains of type IV collagen. These fractions did not show any change after 24 hours exposure to 200 ng/ml of cyclosporin A. These results demonstrate an inhibitory effect of cyclosporin A on collagen synthesis by human umbilical vein endothelial cells. Consequently, matrix accumulation by increased collagen synthesis in cyclosporin A treated patient may not be directly related to the drug effect on endothelial cells.
间质性肾纤维化和牙龈肥大是环孢素A常见的副作用，这被认为与细胞外基质合成功能障碍有关。内皮细胞可能参与了所观察到的基质积聚。我们研究了环孢素A浓度增加对人脐静脉内皮细胞蛋白质合成的影响。在培养基和细胞层中，当环孢素A浓度达到800 ng/ml时，胶原蛋白合成显著下降。从400 ng/ml起，其脯氨酸残基的羟化百分比显著降低。通过SDS-PAGE分析的主要蛋白质是血小板反应蛋白、纤连蛋白以及IV型胶原的α1和α2链。在暴露于200 ng/ml环孢素A 24小时后，这些组分未显示任何变化。这些结果表明环孢素A对人脐静脉内皮细胞的胶原蛋白合成具有抑制作用。因此，在接受环孢素A治疗的患者中，因胶原蛋白合成增加导致的基质积聚可能与药物对内皮细胞的作用没有直接关系。
