GRβ在原发性肾病综合征患儿糖皮质激素耐药中的作用

Effect of glucocorticoid on glucocorticoid-resistant children with primary nephrotic syndrome

目的 研究原发性肾病综合征患儿PBMCsGRβ表达水平与肾组织中原位GRβ表达水平的关系及其在PNS患儿糖皮质激素耐药中的作用。方法 40例原发性肾病综合征患儿分成激素敏感组与激素耐药组,每组各 20例,应用免疫组织化学技术,对其肾活检组织与PBMCs中GRα、GRβ进行检测,应用半定量评分法对各组肾病患儿肾小球与肾小管间质病理改变进行半定量分析。结果 激素耐药组肾小球病理积分与肾小管病理积分高于激素敏感组 (P均 <0.01);激素敏感组与激素耐药组原发性肾病综合征患儿肾活检组织GRα与PBMCs中GRα表达低于正常对照组 (P均 <0.01);激素敏感组与激素耐药组原发性肾病综合征患儿肾活检组织GRβ与PBMCs中GRβ表达高于正常对照组(P均<0.01);中度损害组肾活检组织与PBMCsGRβ表达高于轻度损害组,重度损害组高于中度损害组(P均<0.01);相关分析表明:原发性肾病综合征患儿PBMCs和肾固有细胞GRβ表达明显正相关(r=0. 651; P<0.01), PBMCs和肾固有细胞中GRβ表达与肾脏病理积分正相关(r=0.579, 0.623,P均<0.01)。结论 原发性肾病综合征患儿肾局部、PBMCs中GRβ过表达与PNS患儿糖皮质激素耐药发生有关,与PBMCs和肾局部GRα数目的多少无关,过表达的GRβ可能是通过拮抗GRα的活性影响激素效应的发挥。

Objective Glucocorticoid (GC) is the first therapeutic choice of primary nephro tic syndrome (PNS). The response to GC treatment is an important indicator for the outcome of PNS children. Children with GC-resistant PNS present with incom plete or no response to GC, and may herald the progression to end-stage renal f ailure. However, the detailed mechanism of GC-resistance or GC-sensitive effe ct in these PNS children has not been clearly elucidated. The previous study by the authors indicated that there was increased expression of GRβ in PBMCs in G C-resistant children with PNS, and the over expression of GRβ resulted in GC r esistance via influencing the ability of GRα nuclear translocation. To elucid ate the relationship between GRβ expression in renal and in PBMCs and the effec t of glucocorticoid on glucocorticoid-resistance children with PNS, the express ion of GRα and GRβ in renal tissue and in PBMCs were detected by immunohistoch emistry. Methods Forty children with PNS were divided into two groups, GC-resistant group(20)a nd GC-sensitive group(20), the expression of GRα and GRβ in renal intrinsic cells and in PBMCs were measured with the immunohistochemistry technique. A se miquantitative score was used to evaluate the injury degree of the glomeruli and tubulointerstitium. Results Compared with GC-sensitive group, the glomerular pathologic scores( 6.91±1.98) and renal tubular pathologic scores(7.12±1.62)in GC- resist ant group were significantly different(P<0.01, respectively). GRα expre ssions of renal tissue and PBMCs were higher in the control group(58.3±2.6, 59.1±7.2) than those in the GC-sensitive group(40.2±7.2 and 36.6±5.1 , P<0.01, respectively) and GC-resistant group(35.0±8.2 and 36.4±6 .6, P<0.01, respectively). GRβ expressions of renal tissue and PBMCs we re higher in the GC-resistant group(13.8±3.0 and 12.1±4.1)and in the GC -sensitive group(6.5±1.9 and 5.9±1.0) than that in control group(2.3 ±0.4 and 3.2±1.1, P<0.01, respectively). GRβ expressions in renal t issue and PBMCs were higher in the GC-resistant group than that in the GC-sens itive group(P<0.01). Compared with control group, GRβ expressions in PB MCs and in renal tissue were lower than those in mild renal lesion group( 5.4 ± 2.8, 6.46±2.50), midmedium renal lesion group(8.7±2.4 and 11.4±3 .7)and (17.1±0.4 and 18.7±0.7)in severe renal lesion group(F=5.8 , 15.6, P<0.01, respectively). GRβ expression of PBMCs had a positive correlation with GRβ expression of renal intrinsic cells (r=0.651, P<0 .01). GRβ expressions by PBMCs and renal intrinsic cells were positively corr elated with renal pathologic scores (r=0.579 and 0.623, P<0.0 1, respectively).Conclusion GC-resistant children with PNS were related to the increased GRβ ex pression in PBMCs and renal intrinsic cells. There was no correlation between t he GRα expressions in PBMCs and in renal intrinsic cells. Increased GRβ expre ssion might decrease the effect of GC via inhibiting the activity of GRα.