iTRAQ-based proteomic analysis of hepatic tissues from patients with hepatitis B virus-induced acute-on-chronic liver failure.
iTRAQ-based proteomic analysis of hepatic tissues from patients with hepatitis B virus-induced acute-on-chronic liver failure.
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基于 iTRAQ 的乙型肝炎病毒引起的慢加急性肝衰竭患者肝组织的蛋白质组学分析
DOI：
10.3892/etm.2015.2727
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发表时间：
2015-11
影响因子：
2.7
通讯作者：
Gao ZL
中科院分区：
文献类型：
--
作者：
Peng L;Liu J;Li YM;Huang ZL;Wang PP;Zheng YB;Hua YP;Gao ZL
乙肝病毒引起的急性-慢性肝衰竭(ACLF)是一种严重和普遍的疾病，其发病机制尚不清楚，特别是关于哪些蛋白在疾病过程中表达的问题。本研究的目的是利用基于相对和绝对定量(ITRAQ)的等压标记(ITRAQ)来鉴定正常人和ACLF患者肝组织蛋白表达的差异，并用蛋白质印迹分析来验证结果。采用iTRAQ方法对3例乙肝后急性肝功能衰竭(ACLF)患者和3例正常人肝组织标本进行蛋白质含量分析。对2例乙肝病毒感染的急性肝功能衰竭患者和4例正常人的肝组织进行免疫印迹分析，结果得到了验证。用iTRAQ总共鉴定出57种蛋白质，其≥在乙肝引起的急性肝功能衰竭患者和健康受试者之间的差异是1.5倍。在这57个蛋白中，4个蛋白的表达差异最显著，与肝脏疾病的关系最显著，通过蛋白质印迹分析得到验证：角蛋白，I型细胞骨架19；α-1-酸性糖蛋白1(α1-AGP)；碳酸氢酶-1；以及丝氨酸肽酶抑制物和分支A(α-1抗蛋白酶，抗胰蛋白酶)成员1(SERPINA1)。蛋白质印迹分析结果与iTRAQ结果基本一致。明确乙肝病毒诱导的急性肝功能衰竭患者肝脏蛋白表达的差异，可能为进一步研究急性肝功能衰竭的发病机制提供依据。今后的研究重点应放在α-AGP、碳酸氢酶1和SERPINA1上。
The pathogenesis of hepatitis B virus (HBV)-induced acute-on-chronic liver failure (ACLF), a serious and prevalent medical condition, is not clear, particularly with regard to which proteins are expressed in the course of the disease. The aim of the present study was to identify the differences in hepatic tissue protein expression between normal human subjects and patients with ACLF using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis and to verify the results using western blot analysis. The iTRAQ method was used to analyze the protein contents of hepatic tissue samples from 3 patients with HBV-induced ACLF and 3 normal healthy subjects. The results were verified by subjecting the hepatic tissues from 2 patients with HBV-induced ACLF and 4 healthy subjects to western blot analysis. In total, 57 proteins with ≥1.5-fold differences between patients with HBV-induced ACLF and healthy subjects were identified using iTRAQ. Among these 57 proteins, 4 with the most marked differences in their expression and the most significant association with liver disease were selected to be verified through western blot analysis: Keratin, type-I cytoskeletal 19; α-1-acid glycoprotein 1 (α1-AGP); carbonic anhydrase-1; and serpin peptidase inhibitor and clade A (α-1 anti proteinase, antitrypsin) member 1 (SERPINA1). The results of the western blot analyses were nearly identical to the iTRAQ results. Identifying the differences in liver protein expression in patients with HBV-induced ACLF may provide a basis for studies on the pathogenesis of ACLF. Future studies should focus particularly on α1-AGP, carbonic anhydrase 1 and SERPINA1.