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葶苈大枣泻肺汤对哮喘大鼠尿液代谢组学的调控作用

[Regulatory effect of Tingli Dazao Xiefei Decoction on asthmatic rats by urine metabolomics].

作者信息

Zhang Jin-Ying, Zhou Ning, Wang Yong-Xiang, Cao Yu-Min, Zheng Xiao-Ke, Feng Wei-Sheng

机构信息

College of Pharmacy, Henan University of Chinese Medicine Zhengzhou 450046, China.

College of Pharmacy, Henan University of Chinese Medicine Zhengzhou 450046, China Engineering and Technology Center for Chinese Medicine Development of Henan Province Zhengzhou 450046, China Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province &Education Ministry of China, Henan University of Chinese Medicine Zhengzhou 450046, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2024 Jun;49(12):3312-3319. doi: 10.19540/j.cnki.cjcmm.20231220.401.

Abstract

Urine metabolomics based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was utilized to investigate the metabolic regulation mechanism of Tingli Dazao Xiefei Decoction(TLDZ) in rats with allergic asthma. SD male rats were divided into a normal group, a model group, a dexamethasone group, and a TLDZ group. The allergic asthma model was established by intraperitoneal injection of ovalbumin(OVA) to induce allergy, combined with atomization excitation. Urine metabolites from all rats were collected by UHPLC-Q-TOF-MS. The metabolic profiles of rats in each group were built by principal component analysis(PCA). Besides, the differential metabolites between the model group and the TLDZ group were selected by orthogonal partial least squares discriminant analysis(OPLS-DA), t-test(P<0.05), and variable importance in the projection(VIP) values of more than 3. The differential metabolites were identified through HMDB, METLIN, and other online databa-ses. Heat maps and clustering analysis for relative quantitative information of biomarkers in each group were drawn by MeV 4.8.0 software. Finally, MetaboAnalyst, MBRole, and KEGG databases were used to enrich related metabolic pathways and construct metabolic networks. The result demonstrated that TLDZ could effectively regulate the disordered urine metabolic profiles of asthmatic rats. Combined with multivariate statistical analysis and online databases, a total of 45 differential metabolites with significant changes(P<0.05) between the model group and the TLDZ group were screened out. Metabolic pathways including histidine metabolism, tryptophan metabolism, and arginine and proline metabolism were enriched. TLDZ could improve asthma by regulating related metabolic pathways and interfering with pathological processes such as immune homeostasis airway inflammation. The study investigates the molecular mechanism of anti-asthma of TLDZ from the perspective of urine metabolomics, and combined with previous pharmacological studies, it provides a scientific basis for the clinical development and application of TLDZ in the treatment of asthma.

摘要

基于超高效液相色谱-四极杆飞行时间串联质谱(UHPLC-Q-TOF-MS)的尿液代谢组学被用于研究葶苈大枣泻肺汤(TLDZ)对过敏性哮喘大鼠的代谢调节机制。将SD雄性大鼠分为正常组、模型组、地塞米松组和TLDZ组。通过腹腔注射卵清蛋白(OVA)诱导过敏并结合雾化激发建立过敏性哮喘模型。采用UHPLC-Q-TOF-MS收集所有大鼠的尿液代谢物。通过主成分分析(PCA)构建各组大鼠的代谢谱。此外,通过正交偏最小二乘法判别分析(OPLS-DA)、t检验(P<0.05)和投影变量重要性(VIP)值大于3筛选模型组与TLDZ组之间的差异代谢物。通过HMDB、METLIN等在线数据库鉴定差异代谢物。使用MeV 4.8.0软件绘制各组生物标志物相对定量信息的热图和聚类分析图。最后,利用MetaboAnalyst、MBRole和KEGG数据库富集相关代谢途径并构建代谢网络。结果表明,TLDZ可有效调节哮喘大鼠紊乱的尿液代谢谱。结合多变量统计分析和在线数据库,筛选出模型组与TLDZ组之间共45种有显著变化(P<0.05)的差异代谢物。包括组氨酸代谢、色氨酸代谢以及精氨酸和脯氨酸代谢在内的代谢途径得到富集。TLDZ可通过调节相关代谢途径并干扰免疫稳态、气道炎症等病理过程来改善哮喘。本研究从尿液代谢组学角度探讨了TLDZ抗哮喘的分子机制,并结合既往药理学研究,为TLDZ在哮喘治疗中的临床开发和应用提供了科学依据。

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