Zhang Xiuling, Chen Jinxiang, Gao Ziwen, Qi Hui, Dai Yanhong, She Wandong
Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing City, China.
Department of Otolaryngology-Head and Neck Surgery, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin City, China.
Clin Exp Otorhinolaryngol. 2019 Nov;12(4):367-375. doi: 10.21053/ceo.2018.01298. Epub 2019 Mar 27.
To investigate glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) gene expression and protein levels in peripheral blood mononuclear cells (PBMCs) of patients with severe or profound sudden sensorineural hearing loss (SSNHL) and to explore the roles of GRs and HDAC2 in glucocorticoid (GC) insensitivity.
Fifty-five severe or profound SSNHL patients were enrolled in the study. According to hearing improvement after GC treatment, patients were assigned into two groups: GC-sensitive and GC-resistant. A normal reference group included 20 healthy volunteers without hearing loss. Quantitative real-time polymerase chain reaction and Western blot analyses were used to detect the relative expression of GRα, GRβ, and HDAC2 in PBMCs at the mRNA and protein levels.
The protein levels of GRs and HDAC2 in PBMCs of SSNHL patients were lower than the normal reference values before GC treatment. Compared with the GC-resistant group, both the mRNA and protein levels of GRα and HDAC2 were significantly increased in the GC-sensitive group after GC treatment.
A lack of GRα and HDAC2 induction following steroid treatment in GC-resistant SSNHL patients may play a fundamental mechanistic role in GC insensitivity. Response of GRα and HDAC2 to steroid treatment may, thus, predict the prognosis of hearing improvement in SSNHL patients.
研究重度或极重度突发性聋（SSNHL）患者外周血单个核细胞（PBMCs）中糖皮质激素受体（GR）和组蛋白去乙酰化酶2（HDAC2）的基因表达及蛋白水平，探讨GR和HDAC2在糖皮质激素（GC）不敏感中的作用。
55例重度或极重度SSNHL患者纳入本研究。根据GC治疗后的听力改善情况，将患者分为两组：GC敏感组和GC抵抗组。正常参照组包括20名无听力损失的健康志愿者。采用定量实时聚合酶链反应和蛋白质印迹分析，在mRNA和蛋白水平检测PBMCs中GRα、GRβ和HDAC2的相对表达。
GC治疗前，SSNHL患者PBMCs中GR和HDAC2的蛋白水平低于正常参照值。与GC抵抗组相比，GC敏感组GC治疗后GRα和HDAC2的mRNA和蛋白水平均显著升高。
GC抵抗的SSNHL患者在类固醇治疗后缺乏GRα和HDAC2的诱导，可能在GC不敏感中起基本机制作用。因此，GRα和HDAC2对类固醇治疗的反应可能预测SSNHL患者听力改善的预后。
