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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 To investigate the relationship between the expression of GRβ in PBMCs and the expression of GRβ in renal tissues of primary nephrotic syndrome and its role in glucocorticoid resistance in children with PNS. Methods Forty patients with primary nephrotic syndrome were divided into hormone sensitive group and hormone resistant group, with 20 cases in each group. Immunohistochemistry was used to detect GRα and GRβ in renal biopsy tissues and PBMCs. Semiquantitative Scoring method for each group of children with glomerular and tubulointerstitial pathological changes in semi-quantitative analysis. Results The scores of glomerular pathological score and tubule pathology in steroid-resistant group were higher than those in hormone-sensitive group (all P <0.01). In hormone-sensitive group and steroid-resistant group, the expression of GRα and PBMCs in renal biopsy tissues of children with primary nephrotic syndrome (P <0.01). The expression of GRβ in GRβ and PBMCs of children with primary nephrotic syndrome and steroid-resistant group was higher than that of the normal control group (all P <0.01) . The expression of GRβ in renal biopsy and PBMCs in moderate lesion group was higher than that in mild lesion group and severe lesion group was higher than that in moderate lesion group (all P <0.01). The correlation analysis showed that PBMCs and renal intrinsic The expression of GRβ was positively correlated with the expression of GRβ (r = 0.651; P <0.01). The expression of GRβ in PBMCs and renal intrinsic cells was positively correlated with the pathological score (r = 0.579, 0.623, P <0.01). Conclusion The expression of GRβ in children with primary nephrotic syndrome is associated with glucocorticoid resistance in PBMCs and PBMCs, but not with the number of GRα in PBMCs and the kidneys. The overexpression of GRβ may be related to GRα Activity affect the hormone effect.