儿童原发性肾病综合征激素耐药性与外周血淋巴细胞激素受体mRNA表达水平的相关性

Correlation of glucocorticoid resistance and peripheral blood lymphocyte glucocorticoid receptor mRNA expression in children with primary nephrotic syndrome

目的：探讨原发性肾病综合征（PNS）患儿糖皮质激素（GC）耐药性与糖皮质激素受体mRNA（包括GRα与GRβ）表达的相关性。方法选择2012年6月—2014年12月儿科住院的初诊并予大剂量激素治疗PNS患儿80例作为研究组，按照患儿GC疗效反应分为激素敏感亚组与耐药亚组；另选择正常同龄儿童30例作为健康对照组。于治疗前采取静脉血5 ml，使用荧光定量PCR方法检测并比较外周血单个核细胞（PBMCs）中GRα和GRβ的mRNA表达水平。结果80例PNS患儿中出现GC耐药15例（18．8％），GC敏感65例（81．2％），与健康对照组相比，研究组PBMCs的GRαmRNA、GRβmRNA表达水平均较高，差异均有统计学意义（ P ＜0．05）。与GC耐药亚组相比，GC敏感亚组PBMCs的GRβmRNA表达水平较高，差异有统计学意义（ P ＜0．05），而GRαmRNA表达水平差异无统计学意义（ P ＞0．05）。采用Logistic回归分析校正相关混杂因素后显示，患儿PBMCs的GRβmRNA表达水平是GC耐药性的独立危险因素（OR＝2．17，95％CI 1．17～9．21， P ＜0．05）。结论儿童PNS PBMCs的GRβmRNA表达水平是GC耐药性的独立危险因素，可作为预测GC反应性的临床参考指标。

Objective To investigate the relationship between glucocorticoid （ GC） and the expression of glucocorti-coid receptor mRNA （GR） in patients with primary nephrotic syndrome （PNS）.Methods From June 2012 to December 2014 , 80 cases of newly diagnosed pediatric PNS children who treated with high dose of corticosteroid were enrolled as study group.According to the curative effect of GC , these children were divided into hormone sensitive subgroup and resistance sub-group, and 30 cases normal children of the same age were enrolled as healthy controls .Venous blood was taken at 5 ml before treatment, and the mRNA expression level of GR αand GRβin peripheral blood mononuclear cells （PBMCs） were detected by fluorescence quantitative PCR.Results 80 cases of PNS children had 15 cases of GC resistance（18.8%）,65casesof GC sensitive （81.2%）, compared with the healthy control group, the study group’s PBMCs in GR αmRNA and GR beta mRNA expression levels were higher , the differences were statistically significant （ P 〈0.05）.Compared with the subgroup of GC resistance, GC sensitive subgroup ’ s PBMCs of glucocorticoid receptor beta mRNA expression was higher , and the difference was statistically significant （ P 〈0.05）, and GR mRNA expression level’s differences had no statistical signifi-cance （ P〉0.05）.Using logistic regression analysis adjusted for confounding factors , study group children’s PBMCs of glu-cocorticoid receptor beta mRNA expression levels is independent risk factors of GC resistance （OR=2.17, 95% CI 1.17~9.21, P 〈0.05）.Conclusion PNS children’ s glucocorticoid receptor beta mRNA expression level in PBMCs is an inde-pendent risk factor for GC resistance , may use as a clinical reference index for predicting GC response .