糖皮质激素受体和热休克蛋白90与原发免疫性血小板减少症患者糖皮质激素抵抗关系的研究

摘要

目的 探讨初诊原发免疫性血小板减少症(ITP)患者外周血单个核细胞(PBMC)糖皮质激素(Gc)受体(GR)亚型a、β、γ、p及热休克蛋白90(HSP90)与糖皮质激素抵抗(GCR)的关系.方法 初诊ITP患者40例.28例患者接受泼尼松治疗.根据疗效分为糖皮质激素敏感(GCS)组(22例)和GCR组(6例).以29名健康志愿者为正常对照组.采用实时荧光定量PCR方法检测GRa、GRβ、GRγ、GRp和HSP90 mRNA表达.分析患者组与正常组、GCS组和GCR组GRa、GRβ、GRγ、GRp、HSP90 mRNA和HSP90/GRa的组问表达差异.结果 ITP患者组HSP90 mRNA的表达[0.91(0.48~2.21)]低于正常对照组[1.41(0.83~2.61)](P<0.05).GRa mRNA在GCS组明显高于GCR组(P<0.05),GRβ、GRγ、GRp、HSP90 mRNA的表达和HSP90/GRa在GCS组和GCR组间差异均无统计学意义(P>0.05).结论 初诊ITP患者存在HSP90 mRNA表达的减少.ITP患者的GC抵抗与GRa表达减少有关;GRβ含量极低,可能不介导GC效应.%Objective To investigate the expressions of GRct,GRl3,GR7,GRp and heat shock protein 90(HsP90)in primary immune throm[mcytopenia(ITP)patients and their correlations with glucocorticoid resistance.Methods The expressions of glucocorticoid receptors(GRa,GRβ,GRγ,GRp)mRNA and HSP90 in peripheral blood mononuclear cells of 40 newly diagnosed ITP patients and 29 healthy volunteers were examined by real time PCR.Of them.28 patients received ghcocorticoid(GC)therapy divided into GC sensitive group(GCS)and GC resistant group(GCR)according to GC response.GRa,GRβ,GRγ,GRp,HSP90 mRNA and HSP90/GRa were analyzed in paired groups.Results The expression of HSP90 mRNA was significantly decreased in ITP patients[0.91(0.48-2.21)]than in normal subjects[1.41 (0.83-2.61)](P<0.05).There were no significant differences in mRNA expressions of GRa,GRβ,GRγ,GRp and HSP90/GRot between ITP patients and normal controls.The expression of GRct mRNA in GCS Datients was significant higher than in GCR patients(P<0.05).Moreover,no significant difierences in mRNA expressions of GRl3,GRγ,GRp and HSP90 and the ratio of HSP90 to GRot were observed between GCS and GCR patients.Conclusion The expression of HSP90 mRNA decreased in aduh ITP patients.GC resistance in adull ITP patients was associated with reduced expression of GRa.The very low expression of GRB mRNA may be not involved in GC resistance in aduh ITP.