GRβ在肾病综合征患儿中的表达及影响因素研究

目的:探讨原发性肾病综合征(INS)患儿外周血单个核细胞(PBMC)内糖皮质激素受体β(GRβ)表达的意义, 以及激素抵抗型肾病综合征患者的血清对GRβ表达的影响。方法:采用免疫细胞化学和蛋白质印迹方法检测INS患儿GRβ免疫阳性PBMC(GRβ+PBMC)数目和PBMC细胞核内GRβ蛋白量表达, 通过体外细胞培养检测激素抵抗型INS患儿的血清对正常对照组儿童和激素敏感型INS患儿GRβ+PBMC数目和PBMC细胞核内GRβ蛋白质表达的影响。结果:激素抵抗型INS患儿GRβ+PBMC细胞数和细胞核内GRβ蛋白质表达均明显高于激素敏感型INS患儿(P<0.01);经激素抵抗型INS患儿的血清体外共培养24h后, 正常对照组和激素敏感型INS患儿GRβ+PBMC细胞数和细胞核内GRβ蛋白表达量均显著增加(P<0.01).结论:INS患儿糖皮质激素抵抗可能与GRβ的表达亢进有关, 而血清中的炎症因子可能是诱导GRβ高表达、进而导致继发性糖皮质激素抵抗的一个重要因素。

Expression and effect of glucocorticoid receptor β on children with idiopathic nephrotic syndrome

AIM: To elucidate the significance of glucocorticoid(GC) receptor isoform β(GRβ)in children with idiopathic nephrotic syndrome(INS), and to evaluate the effect of sera from GC-resistant INS on the expression of GRβ. METHODS: The percentage of GRβ positive staining peripheral blood mononuclear cells(PBMC) and the quantity of nuclear protein of GRβ in PBMC were detected by immunocytochemistry and Western blotting assay, respectively. The effect of sera isolated from children with GC-resistant INS on GRβ expression was examined by cell culture in vitro. RESULTS: The number of GRβ positive staining PBMC and the quantity of nuclear protein of GRβ in children with GC-resistant INS were significantly higher than those in patients with GC-sensitive INS(P<0 01). The quantity of GRβ protein in nuclei of PBMC in children with GC-resistant INS was significantly higher than that in normal control and children with GC-sensitive INS. After 24 hours incubation with sera from children with GC-resistant INS, the percentage of GRβ positive PBMC and the quantity of nuclear GRβ protein in children with GC-sensitive INS and normal control increased significantly(P<0.05). CONCLUSION: Increased expression of GRβ is closely related with the GC resistance in children with INS, and high expression of GRβ is mediated, at least in part, by certain humoral factors in the serum.