Cao Wen, Zhou Yan, Li Yan, Zhang Xuerong, He Min, Zang Ning, Zhou Yi, Liao Ming
Department of Pharmacology, Guangxi Medical University, Nanning, China.
Guangxi University Library, Guangxi University, Nanning, China.
Toxicol Lett. 2015 Jan 5;232(1):233-45. doi: 10.1016/j.toxlet.2014.11.009. Epub 2014 Nov 13.
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-β1 (TGF-β1), 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.
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染料木黄酮联合治疗在减轻肝纤维化进展方面是有效的。为了更好地理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中蛋白质的表达谱。联合治疗的抗纤维化作用通过肝脏组织学直接评估，并通过测量血清生化标志物和抗氧化酶间接评估。结果表明，联合治疗可显著改善肝功能，表现为丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、转化生长因子-β1（TGF-β1）和I型胶原水平降低，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）水平升高，以及病理组织损伤减轻。通过iTRAQ鉴定出总共89种对联合治疗有差异表达的蛋白质，它们相互作用并参与不同的生物学过程和途径。通过酶联免疫吸附测定法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质（Tpi1、Txn1、Fgb和F7）。我们的工作为联合治疗抗肝纤维化的分子机制提供了有价值的见解，并且所鉴定的靶点可能对未来肝纤维化的治疗有用。
