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靶向蛋白的定量蛋白质组学分析与 Loki Zupa 汤治疗卵清蛋白诱导的哮喘小鼠相关。

Quantitative proteomic profiling of targeted proteins associated with Loki Zupa Decoction Treatment in OVA-Induced asthmatic mice.

机构信息

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China; Institutes of Integrative Medicine, Fudan University, Shanghai, China.

出版信息

J Ethnopharmacol. 2021 Feb 10;266:113343. doi: 10.1016/j.jep.2020.113343. Epub 2020 Sep 28.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Loki Zupa (LKZP) decoction is one of the herbal prescriptions in traditional Uyghur medicine, which is commonly used for treating airway abnormality. However, underlying pathological mechanism and pathways involved has not been well studied.

OBJECTIVES

In this paper, we aim to further confirmed the anti-inflammatory and anti-fibrotic role of LKZP decoction in airway, and uncover the passible mechanism involved via comprehensive quantitative proteomic DIA-MS analysis.

MATERIALS AND METHODS

Mice asthmatic model was established with sensitizing and challenging with OVA. Lung function, pathological status, and inflammatory cytokines were assessed. Total of nine lung tissues were analyzed using proteomic DIA-MS analysis and 18 lung tissues were subjected to PRM validation.

RESULTS

Total of 704 differentially expressed proteins (DEPs) (363 up regulated, 341 down regulated) were quantified in comparison of asthmatic and healthy mice, while 152 DEPs (91 up regulated, 61 down regulated) were quantified in LKZP decoction treated compared to asthmatic mice. Total of 21 proteins were overlapped between three groups. ECM-receptor interaction was significantly enriched and commonly shared between downregulated DEPs in asthma and upregulated DEPs in LKZP decoction treated mice. Total of 20 proteins were subjected to parallel reaction monitoring (PRM) analysis and 16 of which were quantified. At last, two proteins, RMB 10 and COL6A6, were validated with significant difference (P < 0.001) in protein abundance.

CONCLUSIONS

Our results suggest that attenuated airway inflammation and fibrosis caused by LKZP decoction may associated with ECM-receptor interaction and RMB 10 and COL6A6 may be targeted by LKZP decoction in OVA-induced asthmatic mice.

摘要

民族药理学相关性

洛基祖帕(LKZP)汤是传统维吾尔医学中的一种草药方剂,常用于治疗气道异常。然而,其潜在的病理机制和涉及的途径尚未得到很好的研究。

目的

本文旨在通过综合定量蛋白质组学 DIA-MS 分析进一步证实 LKZP 汤在气道中的抗炎和抗纤维化作用,并揭示可能涉及的机制。

材料和方法

使用 OVA 致敏和激发建立小鼠哮喘模型。评估肺功能、病理状态和炎症细胞因子。使用蛋白质组学 DIA-MS 分析分析了总共 9 个肺组织,并用 PRM 验证了 18 个肺组织。

结果

与健康小鼠相比,哮喘小鼠中共有 704 个差异表达蛋白(DEPs)(363 个上调,341 个下调)被定量,而与哮喘小鼠相比,LKZP 汤治疗的小鼠中共有 152 个 DEPs(91 个上调,61 个下调)被定量。三组之间共有 21 个蛋白重叠。哮喘中下调的 DEPs 和 LKZP 汤治疗中上调的 DEPs 之间共同富集了 ECM-受体相互作用。共有 20 个蛋白进行了平行反应监测(PRM)分析,其中 16 个被定量。最后,有两个蛋白,RMB10 和 COL6A6,在蛋白丰度上有显著差异(P<0.001),得到验证。

结论

我们的结果表明,LKZP 汤减轻气道炎症和纤维化可能与 ECM-受体相互作用有关,在 OVA 诱导的哮喘小鼠中,RMB10 和 COL6A6 可能是 LKZP 汤的作用靶点。

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