Wasilewska Anna, Zoch-Zwierz Walentyna, Pietruczuk Mirosława
1st Department of Pediatrics, Medical University of Białystok, ul. Waszyngtona 17, 15-274, Białystok, Poland.
Eur J Pediatr. 2007 May;166(5):447-52. doi: 10.1007/s00431-006-0256-3. Epub 2006 Sep 22.
The aim of this work was to determine the expression of P-glycoprotein (P-gp) on peripheral lymphocytes (CD3) in children with steroid-dependent nephrotic syndrome (SDNS) during cyclosporine A (CyA) and ACE-inhibitor (ACE-I) treatment. The study group (I) consisted of 20 children with SDNS aged 5-18 years, with a subsequent proteinuria relapse at the time of prednisone dose reduction. All nephrotic syndrome (NS) children were examined three times: A--at proteinuria relapse, before CyA treatment; B--after 3 months; C--after 12 months of CyA administration. The control group (II) consisted of 20 healthy children. CD3/P-gp was measured using a flow cytometry assay. The serum CyA level was assessed by means of the immunofluorescence method. The expression of CD3/P-gp in NS relapse, prior to CyA+ACE-I administration, was much higher (median 9.15%, range 1.50-13.50%) when compared to healthy controls (median 1.20%, range 0.30-5.70%). The absolute number of CD3/P-gp in this examination was almost five times higher when compared to healthy controls (p<0.01). After 3 months of CyA+ACE-I therapy, the expression of CD3/P-gp decreased dramatically and was similar to the controls. Similar results were obtained after 12 months of treatment. A strong negative correlation was found between CD3/P-gp and serum CyA concentration in both examinations (r=-0.624, p<0.01; r=-0.464, p<0.01). We conclude that the results of our studies indicate that CyA+ACE-I in SDNS inhibits the expression of P-gp. CyA is an alternative therapy that may lead to the optimization of glucocorticoid (GC) doses, thus, reducing the risk that is associated with the treatment.
本研究旨在确定环孢素A（CyA）和血管紧张素转换酶抑制剂（ACE-I）治疗期间，激素依赖型肾病综合征（SDNS）患儿外周血淋巴细胞（CD3）上P-糖蛋白（P-gp）的表达情况。研究组（I）由20名年龄在5至18岁的SDNS患儿组成，这些患儿在泼尼松剂量减少时出现蛋白尿复发。所有肾病综合征（NS）患儿均接受了三次检查：A——蛋白尿复发时，CyA治疗前；B——3个月后；C——CyA给药12个月后。对照组（II）由20名健康儿童组成。采用流式细胞术检测CD3/P-gp。通过免疫荧光法评估血清CyA水平。与健康对照组（中位数1.20%，范围0.30 - 5.70%）相比，在CyA + ACE-I给药前的NS复发期，CD3/P-gp的表达要高得多（中位数9.15%，范围1.50 - 13.50%）。此次检查中CD3/P-gp的绝对数量几乎是健康对照组的五倍（p < 0.01）。CyA + ACE-I治疗3个月后，CD3/P-gp的表达显著下降，与对照组相似。治疗12个月后也获得了类似结果。在两次检查中，均发现CD3/P-gp与血清CyA浓度之间存在强烈的负相关（r = -0.624，p < 0.01；r = -0.464，p < 0.01）。我们得出结论，我们的研究结果表明，SDNS中的CyA + ACE-I可抑制P-gp的表达。CyA是一种替代疗法，可能会优化糖皮质激素（GC）剂量，从而降低与治疗相关的风险。
