Integrated metabolomics and network analysis reveal changes in lipid metabolisms of tripterygium glycosides tablets in rats with collagen-induced arthritis.

整合代谢组学和网络分析揭示雷公藤多苷片在胶原诱导性关节炎大鼠体内脂质代谢的变化。

• 影响指数: 6.155
• 发表时间: 2023
• 来源期刊: Comput Struct Biotechnol J
• DOI: 10.1016/j.csbj.2023.02.050
• PMID: 36923473
• 文章类型: Journal Article
• 中科院分区: Q4
• 方向: 生物
• 作者列表: Gao Y,Qian Q,Xun G,Zhang J,Sun S,Liu X,Liu F,Ge J,Zhang H,Fu Y,Su S,Wang X,Wang Q

关键词: CDS, Calibrant Delivery System; CFA, Complete Freund’s adjuvant; CIA, collagen-induced arthritis; CUR, curtain gas; DMARDs, disease-modifying anti-rheumatic drugs; ESI, electrospray ionization; FC, fold change; GS1, nebulizer gas; GS2, heater gas; HMDB, Human Metabolome Database; IDA, Information Dependent Acquisition; IgG, immunoglobulin G; Lipid metabolisms; Metabolomics; Micro-CT, Micro-computed tomography; Network analysis; QC, quality control; RA, rheumatoid arthritis; ROC, Receiver operating characteristic; Rheumatoid arthritis; TGT, Tripterygium glycosides tablets; Tripterygium glycosides tablets; VIP, variable importance in projection

Abstract

Tripterygium glycosides tablets (TGT) are the commonly used preparation for rheumatoid arthritis (RA). However, the changes in TGT on RA are still unclear at the metabolic level. This study aimed to reveal the biological processes of TGT in collagen-induced arthritis (CIA) rats through integrated metabolomics and network analysis. First, the CIA model in rats was established, and the CIA rats were given three doses of TGT. Then, the endogenous metabolites in the serum from normal rats, CIA rats, and CIA rats treated with varying doses of TGT were detected by UHPLC-QTOF-MS/MS. Next, univariate and multivariate statistical analyses were performed to find the differential metabolites. Finally, differential metabolites, metabolic pathways, and hub genes were analyzed integrally to reveal the biological processes of TGT in CIA rats. The paw diameter, arthritis score, immunoglobulin G (IgG) concentration, CT image, and histological assay showed that TGT had evident therapeutic effects on CIA rats. Untargeted metabolomics revealed that TGT could ameliorate the down-regulation of lipid levels in CIA rats. Four key differential metabolites were found including LysoP(18:0), LysoPA(20:4), LysoPA(18:2), and PS(O-20:0/17:1). The glycerophospholipid metabolic pathway was perturbed in treating CIA with TGT. A total of 24 genes, including PLD1, LPCAT4, AGPAT1, and PLA2G4A, were found to be the hub genes of TGT in CIA rats. In conclusion, the integrated analysis provided a novel and holistic perspective on the biological processes of TGT in CIA rats, which could give helpful guidance for further TGT on RA. Future studies based on human samples are necessary.

摘要

雷公藤多苷片（TGT）是类风湿性关节炎（RA）的常用制剂。然而,TGT在RA代谢水平上的变化尚不清楚.本研究旨在通过整合代谢组学和网络分析揭示胶原诱导性关节炎(CIA)大鼠TGT的生物学过程。首先,建立大鼠CIA模型，并给予CIA大鼠三剂TGT。然后，正常大鼠血清中的内源性代谢产物，CIA大鼠，用UHPLC-QTOF-MS/MS检测不同剂量TGT治疗的大鼠。接下来,进行了单变量和多变量统计分析以发现差异代谢物.最后,差异代谢物，代谢途径，并对hub基因进行了整体分析，以揭示TGTinCIA大鼠的生物学过程。爪子直径，关节炎评分,免疫球蛋白G（IgG）浓度，CT图像,组织学分析表明，TGT对CIA大鼠有明显的治疗作用。非靶向代谢组学显示，TGT可以改善CIA大鼠血脂水平的下调。发现了四种关键的差异代谢物，包括LysoP(18:0)，LysoPA（20:4），LysoPA（18:2），和PS（O-20：0/17：1）。用TGT治疗CIA时，甘油磷脂代谢途径受到干扰。共有24个基因，包括PLD1、LPCAT4、AGPAT1和PLA2G4A，被发现是TGTinCIA大鼠的中心基因。总之,综合分析为TGTinCIA大鼠的生物过程提供了一种新颖的整体观点，这可以为RA的进一步TGT提供有益的指导。基于人类样本的未来研究是必要的。