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慢性不可预测轻度应激诱导大鼠高血压的机制:蛋白质组学和靶向代谢组学分析。

The mechanism of chronic unpredictable mild stress induced high blood pressure in rats: a proteomic and targeted metabolomic analysis.

机构信息

Zhanjiang Institution of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang, 524045, China.

School of medicine, Shanghai University, Shanghai, 200444, China.

出版信息

Mol Omics. 2023 Jun 12;19(5):395-403. doi: 10.1039/d2mo00332e.

Abstract

Chronic stress, a leading factor for high blood pressure (BP) and even hypertension, affects health quality seriously. However, the management is rather difficult in our rapidly developing modern society, and the underlying mechanism that caused hypertension remains incompletely understood. In this study, we established a rat model of high BP induced by chronic unpredictable mild stress (CUMS). The results showed that CUMS increased the BP and heart rate, as well as the concentrations of CORT, NA, and ACTH. Based on tandem mass tag (TMT)-labeled proteomics, 13 proteins changed in RVLM. Then, targeted metabolomics together with real-time qPCR were applied to validate the levels of the biomolecules quantitatively. The related molecules were confirmed to reveal that CUMS has a great role in the upregulation of muscle contraction, synthesis of cAMP and transport of metals, while down-regulating ralaxin signaling. This finding facilitates a better understanding of the mechanism of hypertension induced by chronic stress and could provide an insight into the prevention and treatment of hypertension.

摘要

慢性应激是高血压(BP)甚至高血压的一个主要因素,严重影响健康质量。然而,在我们快速发展的现代社会中,管理相当困难,导致高血压的潜在机制仍不完全清楚。在这项研究中,我们建立了慢性不可预测轻度应激(CUMS)诱导的高血压大鼠模型。结果表明,CUMS 增加了 BP 和心率,以及 CORT、NA 和 ACTH 的浓度。基于串联质量标签(TMT)标记蛋白质组学,RVLM 中有 13 种蛋白质发生了变化。然后,应用靶向代谢组学和实时 qPCR 定量验证生物分子的水平。相关分子被证实表明,CUMS 在肌肉收缩、cAMP 合成和金属转运的上调中起着重要作用,而松弛素信号的下调。这一发现有助于更好地理解慢性应激引起的高血压的机制,并为高血压的预防和治疗提供了新的思路。

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