Gonzalez R, Lakhdar B, Redon P, Potaux L, Cambar J, Aparicio M
Service de Néphrologie clinique de l'U.F.R. Médecine-I de l'Université de Bordeaux-II.
C R Acad Sci III. 1990;311(3):109-14.
Cyclosporin (CsA), a potent immunosuppressive agent, can induce severe renal damage, characterized by lesions in the tubulo interstitial region and decreased renal function. Isolated glomeruli can be considered as a fruitful model to evidence the direct effect of drugs at the level of glomerular structures. The present study aims to evidence, in this model, vasoactive response of isolated human renal glomeruli induced by different CsA concentrations. Area changes of such isolated glomeruli can be assessed by a semi-automatic morphometric method, using a video-camera device coupled with a microprocessor (Biocom 2000). Experiments are done under double bind conditions. CsA-induced decrease in glomeruli area is dose- and time-dependent. CsA effect is rapid in that glomerular area is significantly decreased even after 5 min. incubation; vasoconstrictive effect is more important (and maximum) after 10 min. incubation; significant decrease can be noted with 10(-7) M (-11.41%) and 10(-6) M (-10.26%). In conclusion, the isolated glomerulus model allows us to demonstrate the direct vasoconstrictive effect of CsA, that can in part explain the renal functional changes and the acute renal failure often described in human clinic.
环孢素(CsA)是一种强效免疫抑制剂,可导致严重的肾损伤,其特征为肾小管间质区域出现病变以及肾功能下降。分离的肾小球可被视为一种有效的模型,用于证明药物在肾小球结构水平的直接作用。本研究旨在在此模型中证明不同浓度的CsA诱导的人离体肾肾小球的血管活性反应。此类分离肾小球的面积变化可通过半自动形态测量法进行评估,该方法使用与微处理器(Biocom 2000)相连的摄像装置。实验在双盲条件下进行。CsA诱导的肾小球面积减小具有剂量和时间依赖性。CsA的作用迅速,即使在孵育5分钟后肾小球面积也会显著减小;孵育10分钟后血管收缩作用更为显著(且达到最大值);10⁻⁷M(-11.41%)和10⁻⁶M(-10.26%)时可观察到显著减小。总之,离体肾小球模型使我们能够证明CsA的直接血管收缩作用,这在一定程度上可以解释人类临床中经常描述的肾功能变化和急性肾衰竭。