Wan Jia, Sun Wei, Li Xiaohai, Ying Wantao, Dai Jingquan, Kuai Xuezhang, Wei Handong, Gao Xue, Zhu Yunping, Jiang Ying, Qian Xiaohong, He Fuchu
Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing, PR China.
Proteomics. 2006 May;6(9):2886-94. doi: 10.1002/pmic.200500638.
Severe acute respiratory syndrome (SARS) is a severe infectious disease that has affected many countries and regions since 2002. A novel member of the coronavirus, SARS-CoV, has been identified as the causative agent. However, the pathogenesis of SARS is still elusive. In this study, we used 2-D DIGE and MS to analyze the protein profiles of plasma from SARS patients, in the search for proteomic alterations associated with the disease progression, which could provide some clues to the pathogenesis. To enrich the low-abundance proteins in human plasma, two highly abundant proteins, albumin and IgG, were first removed. By comparing the plasma proteins of SARS patients with those of a normal control group, several proteins with a significant alteration were found. The up-regulated proteins were identified as alpha-1 acid glycoprotein, haptoglobin, alpha-1 anti-chymotrypsin and fetuin. The down-regulated proteins were apolipoprotein A-I, transferrin and transthyretin. Most of the proteins showed significant changes (up- or down-regulated) in the progressive phase of disease, and there was a trend back to normal level during the convalescent phase. Among these proteins, the alterations of fetuin and anti-chymotrypsin were further confirmed by Western blotting. Since all the up-regulated proteins identified above are well-known inflammation inhibitors, these results strongly suggest that the body starts inflammation inhibition to sustain the inflammatory response balance in the progression of SARS.
严重急性呼吸综合征(SARS)是一种自2002年以来影响了许多国家和地区的严重传染病。一种新型冠状病毒成员,即SARS-CoV,已被确定为病原体。然而,SARS的发病机制仍然不明。在本研究中,我们使用二维差异凝胶电泳(2-D DIGE)和质谱(MS)分析SARS患者血浆的蛋白质谱,以寻找与疾病进展相关的蛋白质组学改变,这可能为发病机制提供一些线索。为了富集人血浆中的低丰度蛋白质,首先去除了两种高丰度蛋白质,即白蛋白和免疫球蛋白G(IgG)。通过比较SARS患者的血浆蛋白质与正常对照组的血浆蛋白质,发现了几种有显著改变的蛋白质。上调的蛋白质被鉴定为α-1酸性糖蛋白、触珠蛋白、α-1抗糜蛋白酶和胎球蛋白。下调的蛋白质是载脂蛋白A-I、转铁蛋白和甲状腺素转运蛋白。大多数蛋白质在疾病进展期显示出显著变化(上调或下调),并且在恢复期有恢复到正常水平的趋势。在这些蛋白质中,胎球蛋白和抗糜蛋白酶的改变通过蛋白质印迹法进一步得到证实。由于上述所有上调的蛋白质都是众所周知的炎症抑制剂,这些结果强烈表明,在SARS进展过程中,机体启动炎症抑制以维持炎症反应平衡。