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串联质谱标签蛋白质组学分析揭示了博来霉素诱导肺纤维化的机制及人参金银花超微粉茶的作用。

TMT proteomics analysis reveals the mechanism of bleomycin-induced pulmonary fibrosis and effects of Ginseng honeysuckle superfine powdered tea.

作者信息

Li Xiaoli, Yu Xin, Gao Yuan, Zhao Wenqian, Wang Yajuan, Yu Fei, Fu Chunli, Gao Haiqing, Cheng Mei, Li Baoying

机构信息

Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, 250012, China.

Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, 250012, China.

出版信息

Chin Med. 2023 May 24;18(1):60. doi: 10.1186/s13020-023-00769-x.

Abstract

BACKGROUND

Pulmonary fibrosis (PF) is a chronic and potentially fatal lung disease and disorder. Although the active ingredients of ginseng honeysuckle superfine powdered tea (GHSPT) have been proven to have anti-inflammatory and antioxidant effects, the mechanism of GHSPT on PF remains unclear. The present study was to explore the underlying mechanism of GHSPT in treating PF based on proteomics and network pharmacology analysis and to confirm it in vivo.

MATERIALS AND METHODS

We used intratracheal instillation of bleomycin to induce the PF mouse model and GHSPT (640 mg/kg) intragastrically administrated to PF mice for 21 days. The lung tissues were harvested for TMT-based proteomics. The UPLC-Q-Exactive MS/MS analyze the serum migrant compounds of GHSPT in the PF mice. Moreover, components of GHSPT were harvested from the pharmacology database of the TCMSP system. PF-related targets were retrieved using NCBI and GeneCards databases.

RESULTS

Our results showed that GHSPT significantly alleviated PF mice. Proteomics analysis showed that 525 proteins had significantly changed in the lung of untreated PF mice. Among them, 19 differential proteins were back-regulated to normal levels after GHSPT therapy. Moreover, 25 compounds originating from GHSPT were identified in the serum sample. Network analysis showed 159 active ingredients and 92 drug targets against PF. The signaling pathways include apoptosis, ferroptosis, cytokine-cytokine receptor, P53, and PI3K-Akt signaling pathway.

CONCLUSION

The evidence suggests that GHSPT might play an effective role in the treatment of PF by multi-target interventions against multiple signaling pathways.

摘要

背景

肺纤维化(PF)是一种慢性且可能致命的肺部疾病。尽管人参金银花超细粉茶(GHSPT)的活性成分已被证明具有抗炎和抗氧化作用,但其对PF的作用机制仍不清楚。本研究旨在基于蛋白质组学和网络药理学分析探索GHSPT治疗PF的潜在机制,并在体内进行验证。

材料与方法

我们通过气管内注射博来霉素诱导PF小鼠模型,并对PF小鼠灌胃给予GHSPT(640mg/kg),持续21天。收集肺组织进行基于TMT的蛋白质组学分析。采用超高效液相色谱-四极杆-静电场轨道阱串联质谱(UPLC-Q-Exactive MS/MS)分析PF小鼠血清中GHSPT的移行成分。此外,从中药系统药理学数据库(TCMSP)的药理学数据库中获取GHSPT的成分。使用美国国立医学图书馆(NCBI)和基因卡片(GeneCards)数据库检索PF相关靶点。

结果

我们的结果表明,GHSPT显著减轻了PF小鼠的症状。蛋白质组学分析显示,未经治疗的PF小鼠肺中有525种蛋白质发生了显著变化。其中,19种差异蛋白质在GHSPT治疗后恢复到正常水平。此外,在血清样本中鉴定出25种源自GHSPT的化合物。网络分析显示有159种活性成分和92个针对PF的药物靶点。信号通路包括凋亡、铁死亡、细胞因子-细胞因子受体、P53和磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-Akt)信号通路。

结论

证据表明,GHSPT可能通过对多个信号通路的多靶点干预在PF治疗中发挥有效作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa30/10207824/d4663e66c725/13020_2023_769_Fig1_HTML.jpg

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