基于UPLC-Q-exactive-MS的代谢组学和基于iTRAQ的蛋白质组学技术相结合评价滕府降压片的降压作用。

PubMed ID
发表日期 2018年Apr月

原始出处 生物医学与药物疗法
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
作者 Tian  Yanpeng  Jiang  Feng  Li  Yunlun  Jiang  Haiqiang  Chu  Yanjun  Zhu  Lijuan  Guo  Weixing 

文献标题 基于UPLC-Q-exactive-MS的代谢组学和基于iTRAQ的蛋白质组学技术相结合评价滕府降压片的降压作用。
Evaluation of the anti-hypertensive effect of Tengfu Jiangya tablet by combination of UPLC-Q-exactive-MS-based metabolomics and iTRAQ-based proteomics technology.

文献摘要 OBJECTIVE

滕府降压片是由钩藤、莱菔子组成的中药制剂。这是一种医院制剂,广泛用于临床治疗高血压。以前的代谢组学研究表明,TJT通过恢复受损的NO生成,改善炎症状态和血管重构,对高血压起到保护作用。一项临床蛋白质组学研究也揭示了TJT干预过程中的五个关键靶蛋白。本研究的目的是整合蛋白质组和代谢组数据集,以全面了解TJT治疗高血压的分子机制。

METHODS

采用超高效液相色谱-质谱联用技术(UPLC-Q-Exactive-MS)对自发性高血压大鼠和Wistar-Kyoto大鼠的血清样本进行了分析蛋白质组学技术。此外,我们选择了两个候选蛋白,并用酶联免疫吸附试验(ELISA)测定了它们在大鼠血清中的表达水平。

RESULTS

在大鼠血清中共鉴定出20种潜在的生物标志物和14种差异蛋白。这些物质主要参与三种生物学途径:激肽释放酶-激肽途径、脂质代谢途径和PPARγ信号途径。

CONCLUSIONS

结果提示,通脉通脉汤能有效治疗高血压病,部分通过调节上述三种代谢途径。蛋白质组学和代谢组学的结合为揭示TJT对自发性高血压大鼠的干预作用和治疗机制提供了一种可行的方法。


OBJECTIVE

Tengfu Jiangya tablet (TJT) is a traditional Chinese medicine formulation composed of Uncaria rhynchophylla and Semen raphani. It is a hospital preparation that is widely used in clinics for treating hypertension. A previous metabolomics study reported that TJT exerted a protective effect on hypertension by restoring impaired NO production, ameliorating the inflammatory state, and vascular remodeling. A clinical proteomics study also revealed five key target proteins during TJT intervention. This study aimed to integrate proteome and metabolome data sets for a holistic view of the molecular mechanisms of TJT in treating hypertension.

METHODS

Serum samples from spontaneously hypertensive rats and Wistar Kyoto rats were analyzed using ultra-high performance liquid chromatography coupled to Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS)-based metabolomics technology and isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics technology. Moreover, we selected two candidate proteins and determined their expression levels in rat serum using an enzyme-linked immunosorbent assay (ELISA).

RESULTS

A total of 20 potential biomarkers and 14 differential proteins in rat serum were identified. These substances were mainly involved in three biological pathways: the kallikrein-kinin pathway, the lipid metabolism pathway, and the PPARγ signaling pathway.

CONCLUSIONS

The results suggested that TJT could effectively treat hypertension, partially by regulating the above three metabolic pathways. The combination of proteomics and metabolomics provided a feasible method to uncover the underlying interventional effect and therapeutic mechanism of TJT on spontaneously hypertensive rats.


获取全文 10.1016/j.biopha.2018.02.025