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茵陈蒿汤治疗胆管结扎致肝纤维化大鼠后肝脏蛋白质组的变化

Changes of hepatic proteome in bile duct ligated rats with hepatic fibrosis following treatment with Yin-Chen-Hao-Tang.

作者信息

Lee Tzung-Yan, Chang Hen-Hong, Kuo Jong-Jen, Shen Jiann-Jong

机构信息

Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, Chang Gung University, and Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Kwei-Shan Taoyuan 333, Taiwan, ROC.

出版信息

Int J Mol Med. 2009 Apr;23(4):477-84. doi: 10.3892/ijmm_00000154.

Abstract

Yin-Chen-Hao-Tang (YCHT) is recognized as a hepatoprotective agent for various types of liver diseases. Proteomics approaches were used to study hepatic and serum protein expression changes in bile duct ligated (BDL) rats following YCHT treatment for 27 days. Two-dimensional gel electrophoresis was used to analyze proteome changes. Of the proteins that exhibited changes, 17 were identified by means of matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry. The major effect of YCHT was evident in cytoskeleton related protein, plectin-1. In addition, proteins involved in metabolism of lipids were also shown to be affected, including low-density lipoprotein receptor-related protein 2 precursor (glycoprotein 330) and apolipoprotein A-I precursor (ApoA-I). Significant up-regulation of keratin 8 and 19 was found in liver tissue of BDL rats. Supplementation with YCHT also triggered alterations in the above proteins. Interestingly, YCHT treatment caused a statistically significant down-regulation in the secretion of monocyte chemoattractant protein-1 (MCP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in BDL rats with fibrosis. Our results suggested that YCHT may be useful for treatment of liver fibrosis because of its possible antiapoptotic properties, and the therapeutic effects of YCHT on liver diseases might be associated with its lipid biosynthesis regulation.

摘要

茵陈蒿汤被认为是一种对各种肝病具有保肝作用的药物。采用蛋白质组学方法研究了茵陈蒿汤治疗27天后胆管结扎(BDL)大鼠肝脏和血清蛋白表达的变化。使用二维凝胶电泳分析蛋白质组变化。在表现出变化的蛋白质中,有17种通过基质辅助激光解吸/电离飞行时间(MALDI-TOF)质谱法进行了鉴定。茵陈蒿汤的主要作用在细胞骨架相关蛋白网蛋白-1中较为明显。此外,参与脂质代谢的蛋白质也显示受到影响,包括低密度脂蛋白受体相关蛋白2前体(糖蛋白330)和载脂蛋白A-I前体(ApoA-I)。在BDL大鼠的肝组织中发现角蛋白8和19显著上调。补充茵陈蒿汤也引发了上述蛋白质的改变。有趣的是,茵陈蒿汤治疗使纤维化BDL大鼠的单核细胞趋化蛋白-1(MCP-1)和金属蛋白酶组织抑制剂-1(TIMP-1)分泌出现统计学上的显著下调。我们的结果表明,茵陈蒿汤因其可能的抗凋亡特性可能对肝纤维化治疗有用,且茵陈蒿汤对肝病的治疗作用可能与其脂质生物合成调节有关。

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