应用SELDI-TOF-MS筛选矽肺模型大鼠的血清生物标志物及建立血清蛋白指纹分类决策树  

Utilizing SELDI-TOF-MS to screen serum biomarkers and establish serum protein fingerprints for the classification and decision tree of silicoticrats

作　　者：赵学峰[1] 王世鑫[1] 曾家伟[1] 何冰[2] 涂植光[1] 

机构地区：[1]重庆医科大学医学检验系,重庆400016 [2]武警医学院蛋白质组学实验室,天津300162

出　　处：《武警医学院学报》2007年第3期209-215,F0003,共8页Acta Academiae Medicinae CPAPF

基　　金：国家自然科学基金资助项目(30572464);天津市科技攻关培育项目(033106011)

摘　　要：【目的】应用表面增强激光解吸离子化飞行时间质谱(surface enhanced laser desorption-ionization time-of-flight mass spectrometry,SELDI-TOF-MS)技术寻找染矽尘大鼠血清潜在生物标志物,探索建立染矽尘大鼠血清蛋白指纹分类决策树。【方法】128只雄性Wistar大鼠随机分为对照组和染矽尘模型组,以气管暴露法建立矽肺模型,分别在7、14、28和60 d进行腹主动脉采血。采用SELDI-TOF-MS技术以CM10芯片检测大鼠的血清蛋白指纹图谱,用Ciphergen公司专有软件分析数据并建立血清蛋白指纹分类诊断决策树。【结果】与对照组相比,14 d时,m/z 4968.66多肽分子在染矽尘大鼠模型组显著升高(P<0.05);而m/z 9312.29和m/z 9511.19多肽分子分别在28、60 d时显著升高(P<0.05),并均与Ⅰ型胶原增加呈显著正相关(r=0.982,P=0.018;r=0.939,P=0.061);以28、60 d的对照组和染矽尘大鼠组为训练样本,血清蛋白指纹诊断决策树图分类敏感性和特异性分别达100%、83.33%。【结论】m/z 4 968.66多肽分子可作为矽尘所致早期炎症反应的生物标记物,m/z 9312.29、m/z 9511.19多肽分子可能是矽尘所致进行性肺间质纤维化的标志分子。在矽尘暴露28、60d时,血清蛋白指纹分类诊断树的敏感性和特异性分别达100%、83.33%。[Objeaive] To seek serum biomarkers and establish serum protein fingerprints for the classification and decision tree for silicotic rats. [Method] 128 rats were randomly divided into control and silica-treated group. Silicotic rats model were established by direct tracheal instillation of silica. At 7, 14, 28 and 60 d after silica injected, rats were killed and blood were taken. Serum protein fingerprints were detected by SELDI-TOF-MS with CM10 protein-chip, datasets were analyzed and the serum protein fingerprints classification and decision tree was established by patented softwares of Ciphergen Biosystem. [Results] Compared with control group, polypeptide at m/z 4 968.66 was markedly increased in silicotic rats group at 14 d （P 〈 0.05）, and the polypeptides at m/z 9 312.29 and at m/z 9 511. 19 were closely correlated with I type collagen synthesis at 28th and 60th day （ r = 0.982, P = 0.018; r = 0. 939, P = 0.061 ）, and also significantly increased in silicotic rats group （ P 〈 0.05）. It was demonstrated that 83.33 % specificity and 100% sensitivity in serum protein fingerprints clsssification and decision tree constructed by training samples. [Conchusion] It is indicated that the polypeptide at m/z 4 968.66 may be a potential biomarker for early phase silica induced inflammation reaction, polypeptides at m/z 9 312.29 and m/z 9 511.19 may be the potential biomarkers for the progression of pulmonary fibrosis induced by silica. At 28, 60 d of silica exposed rats, the specificity and sensitivity of serum protein fingerprints clsssification and decision tree is 83.33% and 100% respectively.

关 键 词：表面增强激光解吸离子化飞行时间质谱 矽肺 生物标记物 血清蛋白指纹 

分 类 号：R135.2[医药卫生—劳动卫生]