老年性聋易感个体血清差异蛋白的筛选

目的：研究老年性聋（age－related hearing loss ，ARHL）易感个体外周血血清蛋白质组表达变化，筛选差异表达蛋白，建立A R H L易感个体血清蛋白指纹图谱诊断模型。方法选择2015年1～11月年龄大于60岁的非耳科疾病住院患者，对符合条件的78例进行纯音测听及填写问卷调查表，参照声学听阈与年龄关系的统计分布（GB／T 7582－2004／ISO 7029：2000）国家标准将频率特异性听阈转换为Z值（Z值为在给定频率上个体实际听阈与中位听阈的差异），以Z值大于零者为易感组（52例），Z值小于零者为非易感组（26例），应用弱阳离子磁珠加MALDI－TOF MS技术，结合生物资料管理器软件（bio explorer ，BE）筛选老年性聋易感个体血清差异表达蛋白并构建诊断模型。结果得到显著性差异的多肽峰共有9个，分子量分别为4047．1、2957．1、4084．5、4260．1、2102．9、1288、3276、4146．2、3153．4 Da ，其中6个上调，3个下调；选用其中2个建模效果最好的差异蛋白峰（分子量为3276．0、3153．4 Da）建立老年性聋易感个体血清蛋白指纹图谱诊断模型，经盲法验证，该模型的敏感度和特异度分别为68．18％、66．67％，ROC曲线下面积为0．711823，对老年性聋易感者与非易感者有一定的识别能力。结论本研究筛选出了ARHL差异蛋白，建立了首个ARHL易感个体血清蛋白指纹图谱诊断模型，对老年性聋易感者与非易感者有一定的识别能力，为进一步探讨ARHL防治措施提供了数据参考。

The Screening of the Changes of Peripheral Serum Protein Expression in Individuals with Age-related Hearing Loss

Objective In this study ,we studied the changes of peripheral serum protein expression in ARHL susceptible individuals .The differentially expressed proteins were screened .The pathogenesis of ARHL was further explored and the susceptible individual screening strategy was studied .Methods Hospitalized patients without ear diseases from January to November 2015 were studied .Pure tone audiometry was conducted(n=78)with the Z score being calculated for each patient .The patients were divided into susceptible group (n=52) and unsusceptible one (n=26) according to the Z scores .MALDI-TOF MS combined with weak cation bead was used to screen the differ‐ential protein in the susceptible individuals with ARHL .And then the diagnostic model of serum protein fingerprint of ARHL susceptible individuals was established by BE software .Results Nine polypeptides of statistical signifi‐cance were found .Their molecular weights were 4 047 .1 Da ,2 957 .1 Da ,4 084 .5 Da ,4 260 .1 Da ,2 102 .9 Da , 1 288 Da ,3 276 Da ,4 146 .2 Da and 3 153 .4 Da ,respectively .Among these protein peaks ,there were 6 up regula‐ted and 3 down regulated ,which might become the biomarkers of ARHL susceptible individuals .The diagnostic model of serum protein finger print of ARHL susceptible individuals was established by using 2 differentially ex‐pressed proteins of the molecular weights of 3 276 .0 Da and 3 153 .4 Da .The sensitivity and specificity of the model were 68 .18% and 66 .67% respectively in double-blind verification test .The area under the ROC curve was 0 .711 823 .Conclusion The first serum protein fingerprint diagnostic model was established for ARHL susceptible individ‐ual .This study also provided references for searching better prophylactic -therapeutic measures of ARHL .