天津医药 ›› 2015, Vol. 43 ›› Issue (5): 449-452.doi: 10.11958/j.issn.0253-9896.2015.05.001

• 细胞与分子生物学 •    下一篇

肝移植术后急性排斥患者血清的蛋白质组学分析

蒋琪,茹雅维,李克秋,李光△   

  1. 天津医科大学

  • 收稿日期:2015-02-11 修回日期:2015-03-13 出版日期:2015-05-15 发布日期:2015-05-25
  • 通讯作者: 李光 E-mail:heshengguang@hotmail.com E-mail:jiangqi3000@sina.com
  • 作者简介:蒋琪 (1985), 女, 硕士在读, 主要从事器官移植免疫耐受研究
  • 基金资助:
    国家高技术研究发展计划(863计划)资助项目(2012AA021003); 国家自然科学基金资助项目(21177091); 天津市科技计划项目 (12ZCZDSY03400)

Proteomic analysis of the serum from patients with acute rejection after liver transplantation#br# #br#

JIANG Qi, RU Yawei, LI Keqiu, LI Guang△   

  1. Tianjin Medical University, Tianjin 300070, China

  • Received:2015-02-11 Revised:2015-03-13 Published:2015-05-15 Online:2015-05-25
  • Contact: LI Guang E-mail:heshengguang@hotmail.com E-mail:jiangqi3000@sina.com

摘要: 摘要: 目的 寻找与肝移植术后急性细胞排斥反应 (ACR) 相关的血清蛋白标志物, 并初探相应机制。方法 收集 3 例经肝移植手术、 病理证实 ACR 患者血清为 ACR 组; 3 例肝移植术后、 肝功能各项指标达到临床正常值, 预后良好患者血清为 No-ACR 组; 6 例健康体检者血清等量混合后取出 2 份为 Control 组。应用蛋白质组学相关技术对血清蛋白质组进行分离, 同位素标记相对与绝对定量(iTRAQ)技术筛选和鉴定出 3 组间的差异表达蛋白, 并应用 KEGG 和 STRING 软件对其进行功能分析。结果 在 ACR 组与 Control 组间检出 88 个差异表达蛋白, No-ACR 组与 Control 组间检出 39 个, ACR 组与 No-ACR 组间检出 10 个; 对比 88 个和 10 个差异表达蛋白, 共同存在的有 9 个。 88 个差异表达蛋白中 30 个之间有直接的相互作用, 并可被定位于软件中的 13 个信号通路, 其中 14 个 (46.67%) 分布在补体和凝血级联反应通路; No-ACR 组与 Control 组检出的 39 个差异表达蛋白中 10 个有直接相互作用, 其中 9 个集中在补体和凝血级联反应通路。结论 应用蛋白质组学技术鉴定出的 9 种与 ACR 关系密切的差异表达蛋白,可作为开发 ACR 早期诊断标志物的候选蛋白; 补体和凝血级联反应通路在肝移植术后被显著调节, 预示与 ACR 的发生密切相关。

关键词: 肝移植,  血清,  急性细胞排斥反应, 蛋白标志物, 同位素相对标记与绝对定量技术

Abstract: Abstract: Objective To investigate the protein markers that specifically expressed in patients with acute rejection (ACR) after liver transplantation, and to explore preliminarily the mechanisms. Methods Serum samples from three pa⁃ tients with pathologically confirmed ACR after liver transplantation in Tianjin First Central Hospital were collected as ACR group. Three serum samples from patients with normal liver function indicators after liver transplantation were collected as No-ACR group. And six serum samples from healthy examination were mixed with equal amount as healthy control group. Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) was employed to separate, screen and identify the differential⁃ ly expressed proteins between three groups. KEGG and STRING software were applied to deeply analyze the data of three groups. Results A total of 88 differentially expressed proteins were found between ACR group and healthy control group. There were 39 differentially expressed proteins between No- ACR group and healthy control group. Ten differentially ex⁃ pressed proteins were acquired between ACR group and No-ACR group. Comparing 88 and 10 differentially expressed pro⁃ teins, 9 proteins were the same. Among 88 differentially expressed proteins, 30 of them showed a direct interaction, and can be positioned in 13 signaling pathways based on KEGG and STRING software. Fourteen (46.67%) of the 30 proteins were lo⁃ cated in the complement and coagulation cascade pathway. Among 39 differentially expressed proteins, which were detected between No-ACR group and control group, 10 proteins showed a direct interaction including 9 proteins concentrated in the complement and coagulation cascade pathway. Conclusion By proteomic analysis, nine differentially expressed proteins are obtained, which may be regarded as the candidate bio-markers for ACR early diagnosis after liver transplantation. The complement and coagulation cascades system is significantly adjusted after liver transplantation, indicating this pathway plays an important role in the occurrence of ACR.

Key words: liver transplantation, serum,  , biological markers,  , acute cellular rejection, protein biomarkers,  , isobaric tags
for relative andabsolute quantitation