Expression And Clinical Significance Of P-gp170and HSP90in Children With Primary Nephrotic Syndrome

Objective To study the expression of Permeability-glycoprotein170(P-gp170) andHeat Shock Protein90(HSP90) on peripheral blood lymphocytes and kidney tissues ofpatients with Primary Nephrotic Syndrome (PNS)and the role of them on the steriodresistance and its clinical meaning.Method20children with PNS without any glucocorticoid treatment beforeadmission were divided into two groups,10children with steroid-sensitive nephroticsyndrome (SSNS) and10children with steroid-resistant nephrotic syndrome (SRNS)according to their response to glucocorticoid,10healthy children serving as normal controlgroup (Control). Flowcytometry (FCM) were applied to detect the expression of P-gp170and HSP90on peripheral blood lymphocytes at different time point (1. before prednisonetreatment;2.after four weeks’prednisone treatment); Renal biopsy was adopted to getsamples from children with SRNS after four weeks’prednisone treatment，immunohistochemistry was used to detect the expression level of P-gp170and HSP90，fivenormal renal tissues served as control．Results (1)The expression of P-gp170and HSP90on peripheral blood lymphocyteswere found in children with SSNS、SRNS and Control.(2) There were significantdifferences of the expression of P-gp170and HSP90between SSNS、SRNS and Controlbefore treatment(P<0.05).After four weeks’prednisone treatment, the expression ofP-gp170on peripheral blood lymphocytes was rised,but the expression of HSP90wasdeclined than before(both P<0.05).(3) The expresstion of P-gp170and HSP90onperipheral blood lymphocytes in SRNS were higher than SSNS and Control beforetreatment(P<0.05), after four weeks’prednisone treatment,the expression of P-gp170washigher than before(P<0.05),and the expression of HSP90was declined thanbefore(P<0.05),but was still higher than Control(P<0.05).(4) P-gp170mainly wasexpressed in renal tubular and renal interstitial in SRNS and Control, a notable difference was found between proximal and distal tubules in all groups(P<0.05).(5) HSP90mainlywas expressed in glomerular and renal tubular in SRNS and Control, a significantdifference was found between SRNS and Control (P<0.05).(6)Positive linnear correlationsbeween the expression of P-gp170、HSP90on peripheral blood lymphocytes and24-hoururinary protein quantitative were found,(r=0.563,0.785respectively, bothP<0.05), theexpression of P-gp170on peripheral blood lymphocytes in SRNS respectively waspositively related to the renal tissues gray value and pathological integral (r=0.923,0.846respectively，both P<0.05), the expression of HSP90on peripheral blood lymphocytes inSRNS respectively was positively related to the renal tissues gray value and pathologicalintegral (r=0.708,0.726respectively，both P<0.05), pathological integral in SRNS and24-hour urinary protein quantitative had postive relevance(r=0.753, P<0.05).Conclusion (1)Glucocorticoid itself may induce the excessive increase of P-gp170expression on peripheral blood lymphocytes of patients with PNS;(2)A positive correlationis found between the expression of P-gp170in kidney and pathological integral, the highexpression of P-gp170on peripheral blood lymphocytes may take part in the occurrenceand development of glucocorticoid resistance in SRNS patients;(3) The high expression ofHSP90on peripheral blood lymphocytes and kidney tissues may relate to glucocorticoidresistance in SRNS patients;(4) The level of P-gp170and HSP90on peripheral bloodlymphocytes and kidney tissues of the SRNS patients could reflect the severity of thedisease.