难治性突发性聋患者外周血单个核细胞内HDAC2表达与其预后的相关性分析

The Expression of HDAC2 In Peripheral Blood Mononuclear Cells from Patients with Sudden Sensorineural Hearing Loss

后婕;戴艳红;谢利生;周琼琼;佘万东;

1:南京大学医学院附属鼓楼医院耳鼻咽喉科

摘要
目的探讨组蛋白去乙酰化酶2(histone deacetylase 2,HDAC2)水平与突发性聋(sudden sensorineural hearing loss,SSNHL)患者糖皮质激素(glucocorticoid,GC)抵抗的关系。方法选择难治性SSNHL患者20例,所有患耳鼓室内灌注甲强龙20mg/d,连续10天,同时辅以全身静脉滴注营养神经及改善微循环药物。对照组为10例正常听力志愿者。分离所有研究对象的外周血单个核细胞(peripheral blood mononuclear cell,PBMC),提取细胞核蛋白以及总RNA,分别用HDAC2活性检测试剂盒以及real time PCR的方法,检测受试者PBMC中HDAC2的蛋白活性以及HDAC2mRNA的表达情况,并随访SSNHL患者听力,根据听力恢复情况将SSNHL患者分为GC有效组和GC无效组,探讨HDAC2水平与GC抵抗的关系。结果 20例SSNHL患者中,GC有效8例,GC无效12例,治疗前GC有效组及无效组患耳PTA分别为75.21±9.44和80.98±12.73dB HL,治疗后分别为40.83±14.37和77.92±12.25dB HL;治疗前突聋患者HDAC2蛋白活性OD值(GC有效组0.664±0.022,GC无效组0.659±0.043)显著低于对照组(0.726±0.024),而HDAC2mRNA表达量(GC有效组0.079±0.023,GC无效组0.083±0.047)显著高于对照组(0.035±0.022),治疗后,两组患者HDAC2mRNA表达量(GC有效组0.132±0.041,GC无效组0.132±0.048)较治疗前升高,GC有效组患者HDAC2蛋白活性(0.730±0.033)上升并接近正常水平,而GC无效组患者HDAC2蛋白活性(0.647±0.013)无明显变化。结论难治性SSNHL患者对GC不敏感可能与HDAC2蛋白活性降低有关,GC可以促使HDAC2mRNA的表达上调,GC治疗无效的患者体内可能存在某种机制,对HDAC2进行翻译后修饰,使HDAC2蛋白活性降低,从而抑制组蛋白去乙酰化,导致其对激素治疗不敏感。
关键词
突发性聋;糖皮质激素抵抗;外周血单个核细胞;组蛋白去乙酰化-2;翻译后修饰
基金项目(Foundation):
国家自然科学基金项目(81271074);; 江苏省第十批“六大人才高峰项目;; 江苏省临床医学科技专项(BL2014002);; 南京市国际联合研究项目(2012sd311038)联合资助
作者
后婕;戴艳红;谢利生;周琼琼;佘万东;
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