肾病综合征患儿肾组织P-糖蛋白170表达的研究

Role of P-glycoprotein170 in children with nephrotic syndrome

目的检测P-糖蛋白170(P-gp170)mRNA及蛋白在糖皮质激素(GC)敏感和耐药型肾病综合征(NS)患儿肾组织中的分布、表达变化,初探NS患儿肾组织P-gp170表达在GC耐药中的作用。方法2005-09—2006-04在中南大学湘雅二医院住院的初发特发性肾病(INS)患儿34例,按照GC对患儿的疗效分为GC敏感组(SSNS)和GC耐药组(SRNS),分别以免疫组织化学和原位杂交方法检测患儿肾组织P-gp170蛋白及mRNA的表达,6例正常肾组织为对照。结果正常对照组肾组织及NS患儿肾组织中均有P-gp170蛋白及mRNA的表达;正常对照组及NS患儿肾小球均无P-gp170蛋白及mRNA的表达,其蛋白及mRNA均主要表达于肾小管及肾间质,肾小管近端表达多于远端(P<0.01);免疫组化和原位杂交结果均显示SSNS阳性信号表达多于对照组,而SRNS又高于SSNS(P均<0.01);P-gp170蛋白与mRNA的表达成显著正相关(r=0.87,P<0.05)。结论肾脏本身即可合成、分泌P-gp170;P-gp170在正常肾小管的表达可能与某些代谢物质的转运有关;NS患儿肾小管P-gp170表达增高可能与NS本身的状态有关,或者是GC通过诱导P-gp170的表达增高而导致GC耐药;P-gp170表达上调可能为GC耐药的机制之一;检测肾组织P-gp170的表达水平有助于预测NS患儿GC反应差异性。

Objective To observe the distribations and changes of P-glycoprotein170 （P-gp170 ） expression in renal tissues of children with nephrotic syndrome,in order to probe into the role of P-gp170 in mechanism of children with glucocorticoid- resistant nephritic syndrome. Methods Renal biopsy was adopted to get samples from children with NS,immunohistochemistry and in situ hybrodity was used respectively to detect the expression level of P-gp170 protein and mRNA in 34 children with NS, who were divided into two groups , steroid-sensitive nephritic syndrome （ SSNS ） and steroid-resistant nephritic syndrome （SRNS） according to their response to glucocorticoid ;6 normal renal tissues served as control. Results Positive expression of P-gp170 was found both in children with NS and in normal control. All groups showed no expression of P-gp170 in glomeruli,whereas marked expression was seen in tubular cells and interstitium, a notable difference was found between proximal and distal tubules in all groups, P 〈 0. 01. There was a significant difference between SSNS and SRNS, hoth having higher expressions of P-gp170 than that of control, P 〈 0. 01. Positive correlation was found between P-gp170 mRNA and protein, r = 0. 87, P 〈 0. 05. Conclusion Normal renal tissues can produce P-gp170 by means of autocrine or synthesis, which may be associated with the transportation of some metabolin;whereas higher expression of P-gp170 may be associated with nephritic conditions or steroid administration. Upregulation of P-gp170 may play a role in mechanism of children with SRNS. Renal P-gp170 detection can be adopted to tell children with SRNS from SSNS.