激素抵抗型肾病环孢霉素受体的研究

Study of cyclosporin receptor in steroid-resistant children with nephrotic syndrome

目的探讨激素抵抗型肾病患儿血白细胞环孢素受体的表达和临床意义及介导免疫抑制的机理。方法采用逆转录聚合酶链反应(RT-PCR)测定23例激素抵抗型肾病患儿血白细胞中环孢素受体的表达,并与正常儿童作对照。结果不同病理类型激素抵抗型肾病患儿中,系膜增殖性肾小球肾炎血白细胞中环孢素受体呈高表达,微小病变型肾病、膜增殖性肾小球肾炎、局灶节段性肾小球硬化血白细胞中环孢素受体表达差异无显著性。激素抵抗型肾病患儿急性期血白细胞中环孢素亲和素(CyP)mRNA水平高于恢复期与对照组。激素抵抗型肾病患儿以环孢素5mg/(kg·d)口服治疗10～45d后,56.5%完全缓解,17.4%部分缓解。当环孢素血浓度在100～200μg/L范围、环孢素受体呈高水平表达时,激素抵抗型肾病患儿易引起临床缓解。结论激素抵抗型肾病患儿高水平环孢素受体表达时,可给予合适剂量的环孢素A(CyA)治疗;测定环孢素受体表达水平,对肾病的治疗有指导意义。

Objectives To observe the expression of leukocyte cyclosporin receptor in steroid resis- tant children with nephrotic syndrome(NS),and to investigate the clinical significance and the mechanism of cyclosporin-induced immunosuppression.Methods The expressional levels of leukocyte cyclosporin receptor in23children with steroid resistant NS were determined by the reverse transcription polymerase chain reaction(RT-PCR).The results were compared to that in healthy control group.Results The cyclophilin(CyP)bands(408bp)andβ-actin bands(234bp)were seen distinctly.There was a higher expressional level of leukocyte cyclosporin receptor in children with mesangial proliferative glomerulonephritis(MsPGN),but no significant difference in the expression of leukocyte cyclosporin receptor were observed among minimal change nephritic syndrome(MCNS),membranous proliferative glomerulonephritis(MPGN)and focal segmental glomerulonephritis(FSGS).The expressional level of leukocyte CyP mRNA was higher in acute stage than those in either convalescent stage or control group.Clinically,the complete remission rate was57%and the partial remission rate was27%in23children with steroid resistant NS who received10～45days of cyclosporin A(CyA)therapy at an oral dosage of5mg/kg·d.It was noticed that clinical remission could be easily obtained in children with steroid resistant NS when the blood concentration of CyA maintained at a level of100-200μg/L and the expressional level of the leukocyte cyclosporin receptor was higher.Conclusions It is feasible that a proper dosage of CyA can be given to children with steroid resistant NS when there is a higher expressional level of leukocyte cyclosporin receptor.It will be significant guiding the treatment for children with steroid resistant NS.