原发性肾病综合征患儿外周血GRα、GRβ的表达及临床意义

摘要

目的 探讨糖皮质激素受体α(GRα)和β(GRβ)在原发性肾病综合征(PNS)中的作用及其介导耐药的可能机制.方法 选择15例糖皮质激素(GC)敏感型PNS(SSNS)患儿和15例GC耐药型PNS(SRNS)患儿,以及10例健康对照儿童,应用逆转录-聚合酶链式反应(RT-PCR)检测各组外周血单个核细胞(PBMC)中GRα和GRβ mRNA的表达,并分析其与24h尿蛋白定量(24 hUTP)及肾脏病理积分的关系.结果 PNS患儿PBMC中GRα和GRβ均有表达,并以GRα为主；三组间GRα mRNA的表达无差异(P＞0.05)；而SRNS组GRβ mRNA、GRα/GRβ水平均高于SSNS和对照组(P均＜0.05).GRβ mRNA的表达与24 hUTP和病理积分呈正相关(P＜0.05),即GRβ mRNA的表达越高,病理积分越高,病理损伤越大.结论 GRβ mRNA可以作为监测PNS患儿病情以及预后的指标.针对SRNS患儿PBMC中GRβ升高,增加激素受体敏感性,有望为SRNS的治疗提供新的思路.%Objective To investigate the expression of glucocorticoid receptor (GR)α, GFβ in peripheral blood mononuclear cells in patients with primary nephrotic syndrome and the possible mechanism of GRα and GRβ mediated the steroid resistance. Methods Fifteen children with glucoeorticoid-sensitive primary nephritic syndrome (SSNS group) , 15 children with glucocortieoid-resistant primary nephritic syndrome (SRNS group) , and 10 healthy children (control group) were recruited. The expression of GRα and GRβ Mrna in peripheral blood mononuclear cells (PMBC) was detected by reverse transcription polymerase chain reaction. The relationship of the expression of GRα and GRβ with 24 h urinary protein and renal pathological score were analyzed. Results Both GRα and GRβ, mainly GRα, were expressed in PMBC in children with primary nephritic syndrome. The expression of GRα Mrna were not significant different among SRNS, SSNS and control groups (P > 0.05). The expression of GRp Mrna and GRα/GRβ Mrna was significantly higher in SRNS group than that in SSNS and control groups (P < 0.05). The expression of GRβ was positively correlated with 24 h urinary protein and renal pathological score (both P < 0.05). Conclusions The expression of GRβ Mrna can be used as an indicator to monitor the condition and prognosis of children with primary nephritic syndrome. Because the expression of GRβ is increased in SRNS patients, increased sensitivity of hormone receptor is expected to provide new ideas for the treatment of SRNS.