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基于 GC-MS 的肺组织代谢组学分析与网络药理学相结合揭示了蒲地蓝消炎口服液对 LPS 诱导的小鼠肺损伤的可能保护机制。

GC-MS based metabolomic profiling of lung tissue couple with network pharmacology revealed the possible protection mechanism of Pudilan Xiaoyan Oral Liquid in LPS-induced lung injury of mice.

机构信息

Jumpcan Pharmaceutical Co., Ltd, Taixing, Jiangsu Province, PR China.

School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China.

出版信息

Biomed Pharmacother. 2020 Apr;124:109833. doi: 10.1016/j.biopha.2020.109833. Epub 2020 Jan 17.

Abstract

Pudilan Xiaoyan Oral Liquid (PDL) originated from "Pudilan" Classic Recipe of traditional Chinese medicine is one kind of anti-inflammatory Chinese patent medicine recorded in Chinese Pharmacopeia. PDL has been used clinically for treating inflammatory diseases of the respiratory tract. However, due to the complex composition of PDL, its potential anti-inflammation and the mechanism remain unknown. To identify the mechanism of the PDL in the treatment of lipopolysaccharide (LPS)-induced lung injury of mice. The mice models of lung injury were established and the changes of biochemical indices in serum and histopathology were detected to explore the effects of PDL. The approach of GC-MS metabolomics was used to find more significant metabolites, and the metabolic pathways were enriched through MetaboAnalyst. Then network analysis was applied to visualize the protein related to the important metabolites, merging into a protein-metabolite network via Cytoscape. The treatment of PDL could attenuate LPS-induced histopathological damage of lung tissues, followed by reducing pro-inflammation mediators including IL-10, TNF-a and NF-ĸB in serum. 11 potential metabolites were identified in lung tissue through metabolomics, which were significantly regulated to recover by PDL treatment. The correlated network was constructed by integrating potential metabolites and pathways. Aspartate and l-cysteine were selected as key metabolites and correlated proteins such as IL4I1 and ASPA were speculated as the potential target to treat LPS-induced lung injury using PDL. These results demonstrated that PDL might prevent the pathological process of lung injury through regulating the disturbed protein-metabolite network.

摘要

蒲地蓝消炎口服液(PDL)源自于《蒲地蓝》经典中药方剂,是一种被收录在中国药典中的抗炎中药专利药。PDL 已在临床上用于治疗呼吸道炎症性疾病。然而,由于 PDL 成分复杂,其潜在的抗炎作用及其机制尚不清楚。为了确定 PDL 在治疗脂多糖(LPS)诱导的小鼠肺损伤中的作用机制。建立了肺损伤模型,检测血清生化指标和组织病理学变化,探讨 PDL 的作用。采用 GC-MS 代谢组学方法寻找更显著的代谢物,并通过 MetaboAnalyst 对代谢途径进行富集。然后通过 Cytoscape 将与重要代谢物相关的蛋白质进行网络分析,合并成一个蛋白质-代谢物网络。PDL 治疗可减轻 LPS 诱导的肺组织病理损伤,随后降低血清中促炎介质 IL-10、TNF-a 和 NF-ĸB。通过代谢组学在肺组织中鉴定出 11 种潜在的代谢物,这些代谢物通过 PDL 治疗得到显著调节。通过整合潜在的代谢物和途径构建了相关网络。天冬氨酸和 l-半胱氨酸被选为关键代谢物,推测 IL4I1 和 ASPA 等相关蛋白可能是 PDL 治疗 LPS 诱导的肺损伤的潜在靶点。这些结果表明,PDL 可能通过调节紊乱的蛋白质-代谢物网络来预防肺损伤的病理过程。

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