外周血单个核的细胞中糖皮质激素受体亚型与突发性聋预后的相关性

摘要

Objective To explore the correlations between the GR isoforms exprossion level in PBMCs and the prognosis in patients with SSNHL and to study the possible regulating effects of GC treatments on the GR iso forms expression level. Methods Fasting blood samples were harvested from 27 patients with SSNHL. PBMCs were isolated by Ficoll density gradient, and the amount of GRa mRNA, GRβ mRNA and SRp30c mRNA were de termined by the quantitative real time PCR. The patients were followed up for more than 3 months to evaluate their hearing improvements. The patients were classified into GC-sensitive group (15 cases,PTA improvements ≥15 dB) and GC-resistant group (12 cases,PTA improvements <15 dB ). And 6 volunteers with deviation of nasal septum were enrolled as the control group. The statistical difference of the differential mRNA expression of GRarnmRNA, GR β mRNA, SRp30c mRNA in PBMCs and the ratio of GR a mRNA/ GR β mRNA were compared among the three groups, before and after intratympanic GC perfusion by SPSS 18. 0 software. Results A total of 27 pa tients with SSNHL were enrolled in this study. 20 patients received intratympanic GC perfusion and 7 patients re ceived GC treatments in vein. After treatments, 15 patients were GC sensitive and 12 patients were GC resistant ac cording to their hearing improvements. The expression of GRa mRNA was significantly higher than GRβ mRNA, which was significantly associated with the expression of SRp30c mRNA in all the three groups. The expression of GRa mRNA,GRβ mRNA,SRp30c mRNA and the ratio of GRa mRNA/GRβ mRNA before treatments had no statis tical differences among the three groups. The level of GRa mRNA and GRβ mRNA was down- regulated by intra tympanic GC perfusion in GC-sensitive group, but not so in GC-resistant group. Conclusion The different ex pression level of GRa mRNA, GRβ mRNA, SRp30c mRNA and the ratio of GRa mRNA/GRβ mRNA in PBMCs before treatment were not associate with the hearing outcome in this study, and they shouled not be used to predict the hearing recovery in SSNHL patients. But the down-regulated expression of GRa mRNA and GRβ mRNA after intratymanic GC perfusion may indicate a better hearing recovery. Further studies are needed.%目的 探讨外周血单个核的细胞(peripheral blood mononuclear cells,PBMCs)中糖皮质激素受体(glucocorticoid receptor,GR)亚型与突发性聋(sudden sensorineural hearing loss,SSNHL)预后的相关性以及糖皮质激素(glucocorticoid,GC)治疗对GR亚型表达的影响.方法 选择27例应用GC治疗的SSNHL患者,根据听力预后分为有效组(PTA改善≥15 dB)15例和无效组(PTA改善＜15 dB)12例,6例听力正常的鼻中隔偏曲志愿者为对照组.采用实时荧光定量PCR(quantitative real time PCR,QRT-PCR)检测各组对象外周血单个核细胞中的GRα mRNA、GRβ mRNA和SRp30c mRNA的表达水平,并随访3个月以上.分析GRα mRNA、GRβ mRNA、SRp30c mRNA表达量和GRα mRNA/GRβ mRNA比值在有效组、无效组和对照组间的差异以及SSNHL患者GC治疗前后的差异.结果 27例SSNHL患者中采用鼓室灌注GC治疗20例,静脉滴注GC治疗7例,治疗后有效15例,无效12例.有效组、无效组和对照组间PBMCs中GRα mRNA、GRβ mRNA、SRp30c mRNA表达量和GRα mRNA/GRβ mRNA比值比较差异无统计学意义.鼓室灌注GC治疗前后均留取血标本15例,其中有效8例,无效7例,有效组GC灌注后PBMCs中GRα mRNA和GRβ mRNA表达量均较灌注前下降(ZGRα=-2.380,PGRα=0.017; ZGRβ=-2.521,PGRβ=0.012),而无效组GC灌注前后两者的表达差异无统计学意义(P>0.05).结论本组SSNHL患者治疗前PBMCs中GRα mRNA、GRβ mRNA、SRp30c mRNA表达量和GRα mRNA/GRβ mRNA比值均与SSNHL的听力预后无相关性,尚不能用来预测SSNHL患者对GC的敏感性和听力预后;但鼓室灌注GC治疗后GRα mRNA和GRβ mRNA表达量下调可能提示有较好的听力预后.