糖皮质激素吸入治疗对支气管哮喘患者血清蛋白质组的影响  

The effect of inhaled glucocorticoid therapy on serum proteomics of asthmatic patients

作　　者：姜洪娟[1] 张玄[1] 迟翔宇[1] 王建平[1] 王静[1] 窦建明[1] 

机构地区：[1]山东大学附属省立医院保健呼吸科,济南250021

出　　处：《中华结核和呼吸杂志》2014年第4期274-278,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：山东省优秀中青年科学家科研奖励基金（BS2013YY055）;山东省医药卫生科技发展计划项目（2013WS0119）;山东省医药卫生科技发展计划（保健）项目（2013BJYB18）

摘　　要：目的 比较分析支气管哮喘（简称哮喘）患者吸入糖皮质激素（ICS）治疗前后及健康人的血清蛋白质组,筛选在哮喘发病机制及ICS治疗中起关键作用的靶点蛋白质.方法 选择2011年6月至2012年9月就诊于山东省立医院的慢性持续期哮喘患者30例（哮喘组）及健康志愿者30例（对照组）,哮喘组给予规范的ICS治疗8周,收集哮喘组治疗前后及对照组的血清,应用比较蛋白质组学技术,筛选并鉴定差异蛋白质.对ICS治疗前后差异显著的蛋白质进行Western blot验证及ELISA检测,分析其在各组血清中的浓度变化,并与哮喘患者的IgE、嗜酸粒细胞（EOS）、中性粒细胞百分比（NEUT％）、FEV1占预计值％（FEV1％）行相关分析.结果 哮喘组共鉴定出11个差异表达的蛋白质,其中热休克蛋白70（HSP70）、嗜酸粒细胞趋化蛋白（Eotaxin）、维生素D结合蛋白（VDBP）在ICS治疗前后蛋白丰度差异有统计学意义（均P＜0.05）.Western blot验证了HSP70、Eotaxin和VDBP在各组血清中的表达变化与蛋白质组学结果相一致.ELISA数据显示,哮喘组治疗前血清HSP70和Eotaxin水平[分别为（439±103） ng/L和（183±79） ng/L],明显高于对照组[（209±58） ng/L和（91±46）ng/L]（t值分别为5.281、4.972,均P＜0.01）,哮喘组治疗后血清HSP70和Eotaxin水平[分别为（247±96） ng/L和（105±58）ng/L]明显低于治疗前（t值分别为4.157、3.892,均P＜0.01）];哮喘组治疗前血清VDBP水平[（318±115）mg/L]明显低于对照组[（541±98）mg/L]（f=3.878,P＜0.01）,哮喘组治疗后血清VDBP水平[（479±132） mg/L]明显高于治疗前（t=3.572,P＜0.01）.相关分析显示,HSP70与哮喘患者IgE、NEUT％呈正相关,与FEV1％呈负相关（r值分别为0.568、0.613、-0.516,均P＜0.01）;Eotaxin与哮喘患者IgE、EOS呈正相关,与FEV1％呈负相关（r值分别为0.752、0.826、-0.618,均P＜0.01）;VDBP与哮喘患者NEUT％呈负相关,与FEV1％呈正�Objective To screen the biomarkers which may play important roles in the pathogenesis and therapy of asthma by using serum comparative proteomics.Methods From June 2011 to September 2012,30 chronic persistent asthmatic patients （asthma group） and 30 healthy controls （control group） were selected for study in our hospital.All the asthmatic patients were given 8 week-treatment with inhaled glucocorticoids（ICS）.Then comparative proteomics were employed to identify differential proteins in serum samples from the control group,the asthma pre-treatment group and the asthma post-treatment group.The differential proteins which had significant differences before and after ICS therapy were selected for Western blot analysis and ELISA detection.Besides,the correlation between the differential proteins and IgE,eosinophils （EOS）,neutrophil percentage （NEUT％）,and FEV1 ％ were analyzed.Results Eleven differential proteins were identified.Among them,heat shock protein 70 （HSP70）,eosinophil chemotactic protein（Eotaxin） and vitamin D binding protein（VDBP） had significant differences in protein abundance before and after treatment.The differential expression of the 3 proteins in each group was confirmed by Western blot.ELISA data showed that the serum levels of HSP70 and Eotaxin were significantly higher in the asthma pre-treatment group[（439 ± 103）ng/L,（183 ±79）ng/L] than those in the control group [（209 ± 58）ng/L,（91 ± 46） ng/L] （t =5.281,4.972,all P ＜ 0.01）,but significantly lower in the asthma post-treatment group[（247 ± 96）ng/L,（105 ± 58）ng/L] than those in the pre-treatment group（t =4.157,3.892,all P ＜ 0.01）.However,the serum level of VDBP was significantly lower in the asthmatics pre-treatment group [（318 ± 115）mg/L] than that in the control group[（541 ± 98）mg/L] （t =3.878,P ＜ 0.01）,but significantly higher in the asthma post-treatment group [（479 ± 132）mg/L] than that in the pre-treatment group（t =3.572,P ＜ 0.01）.The corr

关 键 词：哮喘 蛋白质组学 糖皮质激素 

分 类 号：R562.25[医药卫生—呼吸系统]