支气管哮喘患者外周血组蛋白去乙酰化酶9的表达及其意义  

Characteristics of histone deacetylase 9 in peripheral blood of patients with bronchial asthma

作　　者：侯小霞[1] 时国朝[1] 万欢英[1] 艾香艳[1] 施宇衡[1] 倪颖梦[1] 汤葳[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院呼吸科,200025

出　　处：《中华结核和呼吸杂志》2012年第5期340-344,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：上海自然科学基金基础重点研究项目（08JC1415200）

摘　　要：目的探讨支气管哮喘（简称哮喘）患者外周血组蛋白去乙酰化酶9（HistoneDeacetylase9，HDAC9）的表达特征及其与Th2、Th17、调节性T细胞的关系。方法选择2010年3月至2011年6月上海瑞金医院呼吸科47例慢性持续期哮喘患者，分为间歇期哮喘组、轻度哮喘组和中重度哮喘组，各组均行肺功能检查和哮喘控制问卷调查哮喘控制情况。并选取20名健康人作为健康对照组。通过分离外周血单个核细胞（PBMCs），Trizol法抽提RNA，采用荧光实时定量方法检测转录因子GATA3、IL4、HDAC9mRNA表达水平。ELISA检测血浆中Th17细胞分泌的主要细胞因子IL-17以及调节性T细胞分泌的主要细胞因子——转化生长因子（TGF）一B表达水平。结果哮喘组PBMCs中GATA3、IL-4mRNA总体相对表达水平分别为28．12±7．57、743．6±312．8高于健康对照组相对表达水平（分别为0．56±0．22、0．74-0．8），差异有统计学意义（U值分别为16．00和37．00，P〈0．01），HDAC9mRNA在间歇期、轻度、中重度哮喘患者中的表达水平分别为3．20±0．50、89．6±18．0和323．0±65．3，呈逐渐上升趋势，各组间差异有统计学意义（H=11．32，P〈0．05）。同时，哮喘患者总体血浆细胞因子IL-17表达水平为83±55，高于健康对照组的344-22（U：153，50，P〈0．01），而TGF一母表达水平下降趋势，组间无统计学差异。HDAC9mRNA表达水平与GATA3mRNA表达水平呈正相关（r=0．482，P〈0．05），与IL-4mRNA表达水平呈正相关（r=0．432，P〈0．05），与IL-17水平呈现正相关（r=0．538，P〈0．05），与TGF—B表达水平呈负相关（r=-0．417，P〈0．05）。在中重度哮喘患者中，HDAC9mRNA水平与肺功能FEV，占预计值％呈负相关（r=-0．657，P〈0．05）。结论哮喘患者PBMCs中HDAC9mRNA表达水平随病情严重程度逐渐升高，其升高不仅与哮喘发病相关的Th2细胞特征性转录因子GATA3、细Objective To investigate the expression pattern of histone deacetylase 9 （HDAC9） in peripheral blood of asthmatics and its effect on immune cells （Th2, Thl7, Tregs ） involved in the pathogenesis of asthma. Methods Forty-seven asthmatics from Ruijin Hospital were recruited and assigned to intermittent, mild and moderate-severe groups. Lung function test and Asthma Control Questionnaire were performed to evaluate asthma control and severity. Twenty healthy donors were enrolled as controls. GATA3, IL-4, and HDAC9 mRNA expression levels were measured by SYRB Green Real-time PCR. The cytokine IL-17-mainly produced by Thl7 cells and TGF-13-mainly produced by Treg cells, were measured by ELISA. Results The GATA3 and IL-4 mRNA expression levels （28.12 ± 7.57 and 743.6 ± 312. 8 ） were up- regulated in asthmatics as compared to the healthy controls [ 0. 56 ± 0. 22, 0. 7 ± 0. 8 （ U = 16.00,37.00, P 〈 0.01 ） ]. The HDAC9 mRNA expression levels of intermittent, mild and moderate-severe groups were 3.20 ± 0. 50, 89. 6 ± 18. 0, 323.0 ± 65.3, respectively, which were associated with the severity of disease（ H = 11.32, P 〈 0. 05 ）. The level of IL-17 in asthmatic group was （ 83 ± 55 ） ng/L, which was up-regulated as compared to the healthy control [ （ 34 ± 22 ） ng/L （ U = 153.50, P 〈 0. 01 ） ]. The level of TGF-[3 was decreased in the asthmatic groups as compared to the healthy control, but the difference did not reach significance. HDAC9 mRNA expression level was positively correlated with GATA3 mRNA expression level （r = 0. 482, P 〈 O. 05 ）, and also with IL-4 mRNA expression （ r = 0. 432, P 〈 0. 05 ） and IL-17 （ r = 0. 538, P 〈 0.05 ） , but negatively correlated with TGF-β（ r = - 0. 417, P 〈 0.05 ） . In patients with moderate-severe asthma, HDAC9 mRNA expression level was negatively correlated with FEV1% （r = -0. 657, P 〈 0.05 ）. Conclusion HDAC9 mRNA expression was up-regulated in peripheral blood of asthmatics, which was not only associate with the

关 键 词：哮喘 组蛋白脱乙酰化基酶类 T淋巴细胞 调节性 

分 类 号：R562.25[医药卫生—呼吸系统]