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基于多组学方法探究归芪益母散对奶牛脂肪肝细胞的调控机制

Investigation of the regulatory mechanisms of Guiqi Yimu Powder on dairy cow fatty liver cells using a multi-omics approach.

作者信息

Li Chenlei, Wang Feifei, Ma Yanfen, Wang Wenjia, Guo Yansheng

机构信息

College of Animal Science and Technology, Ningxia University, Yinchuan, China.

Key Laboratory of Ruminant Molecular and Cellular Breeding of Ningxia Hui Autonomous Region, College of Animal Science and Technology, Ningxia University, Yinchuan, China.

出版信息

Front Vet Sci. 2024 Oct 9;11:1475564. doi: 10.3389/fvets.2024.1475564. eCollection 2024.

DOI:10.3389/fvets.2024.1475564
PMID:39444735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11497463/
Abstract

INTRODUCTION

Fatty liver disease in dairy cows is a metabolic disorder that significantly affects their health and productivity, imposing a notable economic burden on the global dairy industry. Traditional Chinese medicine (TCM), characterized by its multi-component and multi-target features, has shown unique advantages in the prevention and treatment of various diseases. Guiqi Yimu Powder, a traditional TCM formula, enhances growth, boosts production efficiency, and strengthens immune function in livestock by regulating antioxidant along with anti-inflammatory pathways. However, its specific regulatory mechanisms on fatty liver in dairy cows remain unclear. This study aims to investigate the molecular-level effects and potential regulatory mechanisms of Guiqi Yimu Powder in a Trimethylamine N-oxide (TMAO) induced fatty liver cell model of dairy cows.

METHODS

We employed a comprehensive analysis integrating transcriptomics, proteomics, metabolomics, and network pharmacology. An dairy cow fatty liver cell model was established using TMAO to induce lipid accumulation. Cells were treated with the optimal TMAO concentration identified through preliminary experiments, and further divided into a lipid accumulation group and Guiqi Yimu Powder treatment groups. The treatment groups received varying concentrations of Guiqi Yimu Powder (10, 20, 30, 40, or 50 g/L). High-throughput omics sequencing technologies were utilized to perform a comprehensive analysis of the treated cells. Bioinformatics methods were applied to explore the regulatory effects, aiming to elucidate the specific impacts of Guiqi Yimu Powder on lipid metabolism, liver function, and related signaling pathways, thereby providing scientific evidence for its potential application in the prevention and treatment of fatty liver in dairy cows.

RESULTS

Guiqi Yimu Powder treatment significantly affected 1,536 genes, 152 proteins, and 259 metabolites. KEGG enrichment analysis revealed that the significantly altered molecules are involved in multiple pathways related to the pathology of fatty liver, including metabolic pathways, glutathione metabolism, hepatitis B, and AMPK signaling pathway ( < 0.05). Notably, joint analysis highlighted the regulatory mechanisms of Guiqi Yimu Powder on glutathione cycling, with L-5-Oxoproline identified as an important metabolic compound. These findings indicate its impact on oxidative stress, energy metabolism, and liver function, suggesting potential therapeutic applications for fatty liver in dairy cows.

DISCUSSION

This study elucidated the regulatory mechanisms of Guiqi Yimu Powder on fatty liver cells in dairy cows, providing new scientific evidence for its potential application in the prevention and treatment of fatty liver disease.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e6/11497463/b190bce55869/fvets-11-1475564-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e6/11497463/04cf5e9a421d/fvets-11-1475564-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e6/11497463/881eae803735/fvets-11-1475564-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e6/11497463/b190bce55869/fvets-11-1475564-g011.jpg

引言

奶牛脂肪肝是一种代谢紊乱疾病,严重影响奶牛健康和生产性能,给全球乳制品行业带来显著经济负担。中药具有多成分、多靶点特点,在多种疾病防治中显示出独特优势。归芪益母散作为一种中药方剂,通过调节抗氧化和抗炎途径,可促进家畜生长、提高生产效率并增强免疫功能。然而,其对奶牛脂肪肝的具体调控机制尚不清楚。本研究旨在探讨归芪益母散在三甲胺氧化物(TMAO)诱导的奶牛脂肪肝细胞模型中的分子水平作用及潜在调控机制。

方法

我们采用了转录组学、蛋白质组学、代谢组学和网络药理学相结合的综合分析方法。利用TMAO诱导脂质积累建立奶牛脂肪肝细胞模型。通过初步实验确定最佳TMAO浓度处理细胞,并进一步分为脂质积累组和归芪益母散处理组。处理组接受不同浓度的归芪益母散(10、20、30、40或50 g/L)。利用高通量组学测序技术对处理后的细胞进行综合分析。应用生物信息学方法探索调控作用,旨在阐明归芪益母散对脂质代谢、肝功能及相关信号通路的具体影响,从而为其在奶牛脂肪肝防治中的潜在应用提供科学依据。

结果

归芪益母散处理显著影响了1536个基因、152种蛋白质和259种代谢物。KEGG富集分析表明,显著改变的分子涉及多个与脂肪肝病理相关的途径,包括代谢途径、谷胱甘肽代谢、乙型肝炎和AMPK信号通路(P<0.05)。值得注意的是,联合分析突出了归芪益母散对谷胱甘肽循环的调控机制,其中L-5-氧脯氨酸被确定为一种重要的代谢化合物。这些发现表明其对氧化应激、能量代谢和肝功能的影响,提示其在奶牛脂肪肝治疗中的潜在应用价值。

讨论

本研究阐明了归芪益母散对奶牛脂肪肝细胞的调控机制,为其在脂肪肝疾病防治中的潜在应用提供了新的科学依据。

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