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Targeted neurotransmitter metabolomics profiling of oleanolic acid in the treatment of spontaneously hypertensive rats

机译:针对性神经递质的葡萄酸治疗自发性高血压大鼠的靶向神经递质代谢组科分析

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摘要

Essential hypertension (EH) is a prevalent chronic medical condition and a major risk factor for cardiovascular morbidity and mortality. Neurotransmitters are involved in the physiological process of blood pressure regulation in the body. Studies have shown that oleanolic acid (OA) can effectively regulate neurotransmitter-related metabolic disorders caused by EH, but the mechanism is still unclear. Here, we studied the neurotransmitter metabolic profiles in five brain regions by targeted metabolomics approaches in spontaneously hypertensive rats (SHRs) treated with OA and vehicle. Samples from five brain regions (hippocampus, striatum, hypothalamus, temporal lobe, and frontal lobe) were collected from the control group, the spontaneously hypertensive rat (SHR) group, and the OA group. Targeted metabolomics based on UPLC-Q-Exactive-MS was employed to characterize the dramatically changed neurotransmitters in the brain regions of SHRs treated with OA and vehicle. The expressions of the key enzymes involved in the neurotransmitter metabolism were detected by the reverse transcription-polymerase chain reaction (RT-PCR). The metabolomic profiles of SHRs pre-protected by OA were significantly different from those of unprotected SHRs. A total of 18 neurotransmitters could be confirmed as significantly altered metabolites, which were involved in tyrosine and glutamate metabolism as well as other pathways. The results showing seven key enzymes in neurotransmitter metabolism further validated the changes in the metabolic pathways. OA could effectively restore tyrosine metabolism in the striatum and hypothalamus, glutamate metabolism in the hippocampus, striatum and temporal lobe, cholinergic metabolism in the striatum, and histidine metabolism in the hypothalamus due to its inhibition of inflammatory reactions, structural damage of the neuronal cells, and increase in sedative activity. This study indicated that brain region-targeted metabolomics can provide a powerful tool to further investigate the possible mechanism of OA in EH.
机译:基本高血压(EH)是一种普遍的慢性医学病症和心血管发病率和死亡率的主要危险因素。神经递质参与身体血压调节的生理过程。研究表明,OleAlic acid(OA)可以有效地调节由eh引起的神经递质相关的代谢障碍,但该机制仍然尚不清楚。在这里,我们通过用OA和载体处理的自发性高血压大鼠(SHR)中的目标代谢组织方法研究了五个脑区的神经递质代谢谱。从对照组,自发性高血压大鼠(SHR)组和OA组中收集来自五个脑区(海马,纹状体,下丘脑,颞叶和额叶)的样品。基于UPLC-Q-Exactive-MS的靶向代谢组学用于在用OA和载体处理的SHRS的大脑区域中表征显着改变的神经递质。通过逆转录聚合酶链反应(RT-PCR)检测参与神经递质代谢的关键酶的表达。受OA预防的SHR的代谢物谱与未受保护的SHR的肌肉显着不同。可以确认共18个神经递质是显着改变的代谢物,其参与酪氨酸和谷氨酸代谢以及其他途径。显示神经递质代谢中七个关键酶的结果进一步验证了代谢途径的变化。 OA可以有效地在纹状体和下丘脑中恢复酪氨酸代谢,在海马,纹状体和颞叶中的谷氨酸代谢,纹状体中的胆碱能代谢,并且由于其对炎症反应的抑制,神经元细胞的结构损伤而导致的下丘脑中的组氨酸代谢。并增加镇静活动。本研究表明,脑区靶向的代谢组学可以提供强大的工具,以进一步研究欧洲烹饪中OA的可能机制。

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  • 来源
    《RSC Advances》 |2019年第40期|共13页
  • 作者单位

    Shandong Univ Tradit Chinese Med Coll Tradit Chinese Med Sch Pharmaceut Sci Jinan 250355 Shandong Peoples R China;

    Shandong Univ Tradit Chinese Med Experience Ctr Jinan 250355 Shandong Peoples R China;

    Shandong Univ Tradit Chinese Med Experience Ctr Jinan 250355 Shandong Peoples R China;

    Shandong Univ Tradit Chinese Med Experience Ctr Jinan 250355 Shandong Peoples R China;

    Shandong Univ Tradit Chinese Med Coll Tradit Chinese Med Jinan Shandong Peoples R China;

    Shandong Univ Tradit Chinese Med Coll Tradit Chinese Med Sch Pharmaceut Sci Jinan 250355 Shandong Peoples R China;

    Shandong Univ Tradit Chinese Med Experience Ctr Jinan 250355 Shandong Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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