【摘要】：目的探討組蛋白去乙�；�2(histone deacetylase 2,HDAC2)水平與突發(fā)性聾(sudden sensorineural hearing loss,SSNHL)患者糖皮質(zhì)激素(glucocorticoid,GC)抵抗的關(guān)系。方法選擇難治性SSNHL患者20例,所有患耳鼓室內(nèi)灌注甲強(qiáng)龍20mg/d,連續(xù)10天,同時輔以全身靜脈滴注營養(yǎng)神經(jīng)及改善微循環(huán)藥物。對照組為10例正常聽力志愿者。分離所有研究對象的外周血單個核細(xì)胞(peripheral blood mononuclear cell,PBMC),提取細(xì)胞核蛋白以及總RNA,分別用HDAC2活性檢測試劑盒以及real time PCR的方法,檢測受試者PBMC中HDAC2的蛋白活性以及HDAC2mRNA的表達(dá)情況,并隨訪SSNHL患者聽力,根據(jù)聽力恢復(fù)情況將SSNHL患者分為GC有效組和GC無效組,探討HDAC2水平與GC抵抗的關(guān)系。結(jié)果 20例SSNHL患者中,GC有效8例,GC無效12例,治療前GC有效組及無效組患耳PTA分別為75.21±9.44和80.98±12.73dB HL,治療后分別為40.83±14.37和77.92±12.25dB HL;治療前突聾患者HDAC2蛋白活性O(shè)D值(GC有效組0.664±0.022,GC無效組0.659±0.043)顯著低于對照組(0.726±0.024),而HDAC2mRNA表達(dá)量(GC有效組0.079±0.023,GC無效組0.083±0.047)顯著高于對照組(0.035±0.022),治療后,兩組患者HDAC2mRNA表達(dá)量(GC有效組0.132±0.041,GC無效組0.132±0.048)較治療前升高,GC有效組患者HDAC2蛋白活性(0.730±0.033)上升并接近正常水平,而GC無效組患者HDAC2蛋白活性(0.647±0.013)無明顯變化。結(jié)論難治性SSNHL患者對GC不敏感可能與HDAC2蛋白活性降低有關(guān),GC可以促使HDAC2mRNA的表達(dá)上調(diào),GC治療無效的患者體內(nèi)可能存在某種機(jī)制,對HDAC2進(jìn)行翻譯后修飾,使HDAC2蛋白活性降低,從而抑制組蛋白去乙�；�,導(dǎo)致其對激素治療不敏感。
[Abstract]:Objective to investigate the relationship between histone deacetylase 2 (histone deacetylase 2, HDAC 2) and glucocorticoid (glucocorticoid,GC) resistance in patients with sudden deafness (sudden sensorineural hearing loss,SSNHL). Methods 20 patients with refractory SSNHL were enrolled in this study. All patients were infused with prednisolone 20 mg / d for 10 days, supplemented by systemic intravenous infusion of nutritive nerve and drugs to improve microcirculation. There were 10 normal hearing volunteers in the control group. (peripheral blood mononuclear cell,PBMC was isolated from peripheral blood mononuclear cells (PBMCs). Nuclear protein and total RNA, were extracted from peripheral blood mononuclear cells (PBMCs). The protein activity of HDAC2 and the expression of HDAC2mRNA in PBMC were detected by HDAC2 activity kit and real time PCR, respectively. the hearing of SSNHL patients was followed up. SSNHL patients were divided into GC effective group and GC ineffective group according to hearing recovery to explore the relationship between HDAC2 level and GC resistance. Results among 20 patients with SSNHL, GC was effective in 8 cases and GC was ineffective in 12 cases. The PTA of ears in GC effective group and ineffective group were 75.21 鹵9.44 and 80.98 鹵12.73dB HL, respectively after treatment, 40.83 鹵14.37 and 77.92 鹵12.25dB HL;, respectively. The activity of HDAC2 protein in patients with sudden deafness before treatment (GC effective group 0.664 鹵0.022, GC ineffective group 0.659 鹵0.043) was significantly lower than that in control group (0.726 鹵0.024), while HDAC2mRNA expression (GC effective group 0.079 鹵0.023, GC ineffective group 0.083 鹵0.047) was significantly higher than that in control group (0.035 鹵0.022). After treatment, the expression of HDAC2mRNA in the two groups (GC effective group 0.132 鹵0.041, GC ineffective group 0.132 鹵0.048) was significantly higher than that before treatment. The activity of HDAC2 protein in GC effective group (0.730 鹵0.033) increased and approached the normal level, but there was no significant change in HDAC2 protein activity in GC ineffective group (0.647 鹵0.013). Conclusion the insensitivity to GC in patients with refractory SSNHL may be related to the decrease of HDAC2 protein activity. GC can up-regulate the expression of HDAC2mRNA. There may be some mechanism in patients with ineffective GC treatment. Post-translation modification of HDAC2 can reduce the activity of HDAC2 protein, thus inhibiting histone deacetylation and insensitive to hormone therapy.
【作者單位】： 南京大學(xué)醫(yī)學(xué)院附屬鼓樓醫(yī)院耳鼻咽喉科;
【基金】：國家自然科學(xué)基金項目(81271074) 江蘇省第十批“六大人才高峰項目 江蘇省臨床醫(yī)學(xué)科技專項(BL2014002) 南京市國際聯(lián)合研究項目(2012sd311038)聯(lián)合資助
【分類號】：R764.437

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