Expression Of MDR1 And P-gp170 In Children With Steroid-resistant Nephrotic Syndrome And Its Clinical Meaning

Objective To study the expression of MDR1mRNA and P-gp170 on Peripheral Blood Mononuclear Cell(PBMC) of patients with PNS at different time point,to observe the distributions and changes of P-glycoproteinl70(P-gpl70)expression in renal tissue of children with nephrotic syndrome, to investigate the role of MDR1 and P-gp170 in mechanism of children with SRNS and its clinical meaning.Method 20 children with PNS without any glucocorticoid treatment before admission were divided into two groups, 10 children with steroid-sensitive nephrotic syndrome and 10 children with steroid- resistant nephrotic syndrome according to their response to glucocorticoid ,10 healthy children serving as control. Reverse transcription-polymerase chain reaction (RT-PCR) and flowcytometry (FCM) were applied to detect the expression of MDR1mRNA and P-gp170 on PBMC at different time point (1.before prednisone treatment; 2.after four weeks of prednisone treatment); Renal biopsy was adopted to get samples from 10 children with SRNS after four weeks of prednisone treatment,5 normal renal tissues served as control ,immunohistochemistry was used to detect the expression level of P-gpl70 in the renal tissues.Results (1). Expression of MDR1mRNA and P-gp170 on PBMC were found both in children with PNS and in normal control. A positive correlation was found between MDR1mRNA expression and P-gp170 expression on PBMC(r=0.853,P<0.05).(2)Before the usage of GC, the expression of MDR1mRNA and P-gp170 on PBMC in SRNS patients was obviously higher than the contro(P<0.01), and there is a significant difference between SSNS group and normal group(P<0.05).(3)The expression of MDR1mRNA and P-gp170 in SRNS patients were both significantly higher than that in SSNS group and normal group at each time point (P<0.05).(4)The expression of P-gp170 was shown in renal tissues of healthy children and children with PNS, and marked expression was seen in tubular cells and interstitium,a notable difference was found between proximal and distal tubules in all groups(P<0.05). There is significant difference of P-gp170 expression in proximal tubules of renal tissues between SRNS group and normal group(P<0.05); No expression of P-gp170 was shown in glomeruli of renal tissues..(5)The P-gp170 expression on PBMC and in renal tissues in SRNS patients had positive correlation with kidney pathology score(r=0.449,0.499, P<0.05). (6)The P-gp170 expression in renal tissues had positive correlation with the expression on PBMC in the children with SRNS(r=0.532, P<0.05).Conclusion (1) The expressions of MDR1mRNA and P-gp170 were detected both in PNS patients and healthy children. A positive correlation was found between MDR1mRNA expression and P-gp170 expression on PBMC. (2) The expression of P-gp170 was shown in renal tissues of healthy children and children with PNS, and marked expression was seen in tubular cells and interstitium,a notable difference was found between proximal and distal tubules in all groups. No expression of P-gp170 was shown in glomeruli of renal tissues.(3)The expression of P-gp170 and MDR1mRNA on PBMC in SRNS group was significantly higher than that of SSNS group. There is significant difference of P-gp170 expression in proximal tubules of renal tissues between SRNS group and normal group. The expression of P-gp170 in renal tissues had positive correlation with that on PBMC in SRNS group. The high P-gp170 expression in renal tissues and on PBMC may contribute to the GC resistance in PNS patients, and it may be severed as one possible mark of GC resistance. Intervention of the expression of P-gp170 may provide new thoughts of the treatment of SRNS.