A proteomics-based study of the mechanism of oxymatrine to ameliorate hepatic fibrosis in mice

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS Journal of Chromatography B Pub Date : 2024-08-30 DOI:10.1016/j.jchromb.2024.124280

Jing Wu , Xueqin Jin , Weihua Li , Enqi Liu

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Abstract

Objective

This study investigated the protective effect of oxymatrine (OMT) on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in mice and explored its possible targets and signaling pathways.

Methods

Male BALB/c mice were randomly divided into blank control, model, positive drug (silymarin), and OMT administration groups, respectively, with 10 mice in each group. Hepatic fibrosis was induced in mice using CCl₄ and the corresponding drug intervention was given. After the final administration, ultrasonography tests, blood tests, and analysis of liver differential proteins using tandem mass tag labeling and liquid chromatography-mass spectrometry were performed.

Results

OMT intervention ameliorated CCl₄-induced hepatic fibrosis in mice, significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels, down-regulated the expression of fibrosis factors, such as type IV collagen IV, laminin, type III procollagen III, and alpha-smooth muscle actin, and improved liver function. The results of the proteomic analysis showed that the intervention of OMT significantly down-regulated 130 out of 440 up-regulated proteins and up-regulated 70 out of 294 down-regulated proteins, primarily involving the transient receptor potential (TRP) signaling pathway, the peroxisome proliferator-activated receptors (PPAR) signaling pathway, and the metabolic pathway of arachidonic acid. The main differential proteins involved were Cyp2c37, SCP-2, and Tbxas1. In addition, OMT intervention significantly reversed the expression of sterol carrier protein-2 (SCP2) and upregulated the expression of peroxisome proliferator-activated receptor gamma, Cyp2c37, and transient receptor potential cation channel subfamily V member 1 proteins.

Conclusion

OMT inhibited the proliferative capacity of hepatic stellate cells, induced apoptotic properties, and suppressed the development of fibrosis by elevating Cyp2c37/TRP signaling axis activity and upregulating PPAR pathway activity by inhibiting SCP2.

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基于蛋白质组学的氧化苦参碱改善小鼠肝纤维化机制研究

方法将雄性BALB/c小鼠随机分为空白对照组、模型组、阳性药物（水飞蓟素）组和OMT给药组，每组10只。用 CCl4 诱导小鼠肝纤维化，并给予相应的药物干预。最后给药后，进行超声波检查、血液检查，并使用串联质量标记和液相色谱-质谱法分析肝脏差异蛋白。结果OMT干预改善了CCl4诱导的小鼠肝纤维化，显著降低了血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平，下调了纤维化因子（如IV型胶原IV、层粘连蛋白、III型原胶原III和α-平滑肌肌动蛋白）的表达，并改善了肝功能。蛋白质组分析结果显示，OMT的干预显著下调了440个上调蛋白中的130个，上调了294个下调蛋白中的70个，主要涉及瞬时受体电位（TRP）信号通路、过氧化物酶体增殖激活受体（PPAR）信号通路和花生四烯酸代谢通路。参与其中的主要差异蛋白是 Cyp2c37、SCP-2 和 Tbxas1。此外，OMT干预还能明显逆转固醇载体蛋白-2（SCP2）的表达，并上调过氧化物酶体增殖激活受体γ、Cyp2c37和瞬态受体电位阳离子通道V亚家族成员1蛋白的表达。结论OMT通过提高Cyp2c37/TRP信号轴活性和抑制SCP2上调PPAR通路活性，抑制了肝星状细胞的增殖能力，诱导了细胞凋亡特性，并抑制了肝纤维化的发展。

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.