P300在肾病综合征糖皮质激素耐药中的作用

Role of P300 in steroid-resistant children with primary nephrotic syndrome

目的观察原发性肾病综合征(PNS)激素敏感与激素耐药组P300表达的差异,探讨P300在肾病综合征糖皮质激素耐药中的作用,为揭示PNS激素耐药发生机制提供理论依据。方法采用免疫组化法检测正常对照组肾组织及40例PNS患儿(激素敏感组20例,激素耐药组20例)肾活检组织中P300表达差异。结果正常肾组织仅偶见肾小管上皮细胞P300呈阳性表达;PNS患儿肾组织均存在不同程度P300表达,主要分布于肾小管上皮细胞,肾小球系膜区表达微弱或未表达,其他肾固有细胞未见P300表达;激素敏感组肾小管上皮细胞P300表达较激素耐药组明显增多(P<0.01),P300表达密集部位的肾小管形态正常,结构完整;肾小管上皮细胞P300阳性表达与肾小管间质病理积分呈负相关(P<0.01)。结论P300蛋白主要通过肾小管上皮细胞促进GC效应发挥;PNS患儿肾小管上皮细胞P300表达下降,可能是导致GC耐药及增加GC对肾小管上皮细胞损伤的机制之一。

Objective To investigate the difference of P300synthesis in steroid_sensitive or steroid_resistant children with primary nephrotic syndrome(PNS),and to evaluate the role of P300in steroid reˉsistance in order to provide the mechanism for steroid resistance in children with PNS.Methods The synthesis of P300was detected with the immunohistochemistry way in renal biopsy tissues obtained from20steroid-sensitive PNS children,20steroid-resistant PNS children and5children without PNS as normal control group,respectiveˉly.Results The positive P300in epithelial cells of renal tubules was rare in normal renal tissues of the control group.However,the positive P300could be found in all renal tissues of PNS,mainly in epithelial cells of renal tubules.There were only weak or no synthesis in areas near glomerular mesangium.No P300synthesis was found in other renal proprius cells.P300synthesis in epithelial cells of renal tubules in steroid_sensitive group was more intense than that in steroid_resistant group.Renal tubules with intense P300synthesis presented with normal structure and morphology.The positive synthesis of P300in epithelial cells of renal tubules correlated inversely with pathological scores(P<0.01).Conclusions P300enhanced glucocorticoid effect through tubular epithelia.Down regulation of P300synthesis in epithelial cells of renal tubules was probably one of the mechanism of steroid-resistance and epithelial damage of renal tubules caused by glucocorticoid use.