Naumovic Radomir, Jovovic Djurdjica, Basta-Jovanovic Gordana, Miloradovic Zoran, Mihailovic-Stanojevic Nevena, Aleksic Tamara, Jovanovic Dijana
Clinic of Nephrology, Clinical Center of Serbia, Belgrade, Serbia.
Am J Nephrol. 2007;27(4):379-89. doi: 10.1159/000103918. Epub 2007 Jun 13.
BACKGROUND/AIM: The effects of rapamycin (RAPA) were examined in active Heymann nephritis (HN), an experimental model of human membranous nephropathy (MN). Current opinion on the therapy of MN is controversial, and medications used for its treatment have not yielded the expected results.
In a two-part study, we examined the effects of RAPA (1.5 mg/kg/day) during the induction phase of HN and on the evolving disease. In both parts, control groups of immunized rats not treated with RAPA and control groups of unimmunized rats were observed and sacrificed concurrently with the treated groups.
During the induction phase no significant changes in proteinuria were observed in the group treated with RAPA, in comparison to those in the untreated group (p < 0.001). During the evolving disease RAPA significantly lowered proteinuria (p < 0.001). The characteristic pathohistologic changes and IgG depositions along the glomerular basement membrane were considerably diminished, and infiltration of CD8+ cells completely prevented.
RAPA demonstrated beneficial effects on disease progression, given either in the induction phase or during evolving HN. It would be desirable to investigate the effect of RAPA on patients with MN.
背景/目的:在人类膜性肾病(MN)的实验模型——活动性海曼肾炎(HN)中研究了雷帕霉素(RAPA)的作用。目前关于MN治疗的观点存在争议,用于其治疗的药物尚未取得预期效果。
在一项分为两部分的研究中,我们研究了RAPA(1.5毫克/千克/天)在HN诱导期以及对疾病进展过程中的作用。在两部分研究中,未用RAPA治疗的免疫大鼠对照组和未免疫大鼠对照组与治疗组同时进行观察和处死。
在诱导期,与未治疗组相比,用RAPA治疗的组蛋白尿无显著变化(p < 0.001)。在疾病进展过程中,RAPA显著降低了蛋白尿(p < 0.001)。特征性的病理组织学变化以及沿肾小球基底膜的IgG沉积明显减少,并且完全阻止了CD8 +细胞浸润。
无论是在诱导期还是在进展期的HN中给予RAPA,均显示出对疾病进展的有益作用。研究RAPA对MN患者的影响是可取的。