糖皮质激素受体与特发性血小板减少性紫癜患者激素抵抗的相关性

A study on the relationship between α-and β-isoform of glucocorticoid receptors and glucocorticoid-resistant idiopathic thrombocytopenia purpura

目的 探讨特发性血小板减少性紫癜(ITP)患者外周血单个核细胞(PBMC)内两种糖皮质激素受体(GR)α和β表达水平与糖皮质激素治疗效应之间的关系。方法 采用半定量RT PCR检测不同激素效应ITP患者和正常对照组GRα、βmRNA,采用免疫细胞化学方法检测GRα、β蛋白的表达。结果 (1)ITP激素敏感组、激素抵抗组及正常人体内均有GRα、βmRNA的表达,但以GRα为主, 其GRα/葡萄糖3磷酸脱氢酶(GAPDH)mRNA分别为1 15 ±0 75, 1 63±0 78, 1 27±0 51;(2)激素抵抗组GRβmRNA表达明显高于激素敏感组及正常对照组(P<0 05 ),其GRβ/GAPDHmRNA分别为1 42±0 73, 0 82±0 59, 0 80±0 68; (3)免疫细胞化学结果显示,激素抵抗组GRβ阳性细胞数明显高于激素敏感组及正常对照组(P<0 01 ),分别为28 8±9 9, 5 9±3 2, 5 5±6 8。结论 ITP患者糖皮质激素抵抗可能与GRβ的表达亢进有关。

Objective To clarify the relationship between the expression of α- and β-isoforms of glucocorticoid receptors (GR)and response to glucocorticoid in peripheral blood mononuclear cell(PBMC) of patients with idiopathic thrombocytopenia purpura(ITP) Methods Semi-quantitative RT-PCR was used to detect the expression of GRα、β in PBMC of patients with ITP and to observe the different responses to glucocorticoid in controls Immunocytochemical assay was used to detect the expression of protein of GRα and GRβ Results (1)The expression of GRα mRNA was detected in a sensitive group and a resistant group of patients with ITP and all the controls with GRα/GAPDH mRNA 1 15 ±0 75,1 63±0 78,1 27±0 51 respectively (2)The expression of GRβ mRNA in PBMC in the resistant group of patients with ITP was significantly higher than that in the sensitive group and the controls( P <0 05), with GRβ/GAPDH mRNA 1 42±0 73,0 82±0 59,0 80±0 68 respectively (3)The number of GRβ-positive PBMC in the resistant group was significantly higher than that in the sensitive group and the controls( P <0 01),with the number of GRβ- positive PBMC 28 8±9 9,5 9±3 2,5 5±6 8 respectively Conclusion It is shown that the excessive expression of GRβ may serve as a novel predictor of glucocorticoid resistance in patients with ITP