iTRAQ-based proteomic analysis of combination therapy with taurine, epigallocatechin gallate, and genistein on carbon tetrachloride-induced liver fibrosis in rats
iTRAQ-based proteomic analysis of combination therapy with taurine, epigallocatechin gallate, and genistein on carbon tetrachloride-induced liver fibrosis in rats
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DOI：
10.1016/j.toxlet.2014.11.009
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发表时间：
2015-01-05
影响因子：
3.5
通讯作者：
Liao, Ming
中科院分区：
文献类型：
--
作者：
Cao, Wen;Zhou, Yan;Liao, Ming
在我们之前的研究中，牛磺酸、表没食子儿茶素没食子酸酯和金雀异黄酮的联合治疗可有效缓解肝纤维化的进展。为了更好地了解联合治疗的抗纤维化机制，采用基于 iTRAQ 的蛋白质组学方法研究联合治疗后四氯化碳诱导的肝纤维化大鼠的蛋白质表达谱。联合治疗的抗纤维化作用通过肝脏组织学直接评估，并通过血清生化标志物和抗氧化酶的测量间接评估。结果显示，联合治疗可显着改善肝功能，降低丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、转化生长因子-β1（TGF-β1）和I型胶原水平，提高总抗氧化能力（T-AOC）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）水平，减少病理组织损伤。 iTRAQ 共鉴定出 89 个联合治疗反应的差异表达蛋白，这些蛋白彼此相互作用并参与不同的生物过程和途径。通过酶联免疫吸附试验验证了参与抗氧化防御系统、糖酵解途径和凝血级联途径的四种差异表达蛋白（Tpi1、Txn1、Fgb 和 F7）。我们的工作为抗肝纤维化联合治疗的分子机制提供了有价值的见解，并且确定的靶点可能对未来肝纤维化的治疗有用。 (C) 2014 Elsevier Ireland Ltd. 保留所有权利。
Combination therapy with taurine, epigallocatechin gallate, and genistein was effective in alleviating the progression of liver fibrosis in our previous study. To better understand the anti-fibrotic mechanisms of combination therapy, an iTRAQ-based proteomics approach was used to study the expression profiles of proteins in carbon tetrachloride-induced liver fibrosis rats following combination therapy. The anti-fibrotic effects of combination therapy were assessed directly by liver histology, and indirectly by measurement of serum biochemical markers and antioxidant enzymes. The results showed that combination therapy could significantly improve the liver function, as indicated by decreasing levels of alanine aminotransferase (ALT), aspartate transaminase (AST), transforming growth factor-beta 1 (TGF-beta 1), and collagen I, increasing levels of total antioxidative capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), and reducing the pathological tissue damage. A total of 89 differential expressed proteins in response to combination therapy were identified by iTRAQ, which were interacted with each other and involved in different biological processes and pathways. Four differentially expressed proteins (Tpi1, Txn1, Fgb, and F7) involved in antioxidant defense system, glycolysis pathway and coagulation cascade pathway were validated by enzyme-linked immunosorbent assay. Our work provided valuable insights into the molecular mechanism of combination therapy against liver fibrosis, and the identified targets may be useful for treatment of liver fibrosis in future. (C) 2014 Elsevier Ireland Ltd. All rights reserved.