钩藤对自发性高血压大鼠神经递质昼夜代谢稳态调节的药效学研究。

PubMed ID
G H
发表日期 2020年Nov月

原始出处 生物医学与药物治疗
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
作者 Sun  Mengjia  Wang  Huanjun  Gong  Lili  Qi  Dongmei  Wang  Xiaoming  Li  Yunlun  Jiang  Haiqiang 

文献标题 钩藤对自发性高血压大鼠神经递质昼夜代谢稳态调节的药效学研究。
A novel time-dimension and circadian rhythm-dependent strategy for pharmacodynamic evaluation of Uncaria in the regulation of neurotransmitter circadian metabolic homeostasis in spontaneously hypertensive rats.
A novel time-dimension and circadian rhythm-dependent strategy for pharmacodynamic evaluation of Uncaria in the regulation of neurotransmitter circadian metabolic homeostasis in spontaneously hypertensive rats.

文献摘要

在本研究中,我们旨在利用代谢组学平台研究24小时内受昼夜节律调节的神经递质以及钩藤给药对每日节律的影响,以建立一种评价钩藤时空疗效的评价策略。采用靶向超高效液相色谱-质谱代谢组学方法,每4小时定量检测32种神经递质代谢物 24小时以上 H为了评估24小时代谢物节律,我们进行了余弦分析。逆转录聚合酶链反应(RT-PCR)检测下丘脑节律基因的表达。结果显示,在整个昼夜节律周期内,M组血清中多种神经递质昼夜节律性丢失,提示高血压可引起昼夜节律紊乱。对三组中32种神经递质水平的节律振荡进行余弦分析表明,代谢物节律在一天中的大致相同时间达到峰值(ZT4和ZT16)。此外,代谢节律的振幅也发生了改变。钩藤治疗后,13种神经递质波幅恢复正常。下丘脑节律基因的变化趋势证实了神经递质的节律变化。建立了一种新的药效学评价策略,在24小时内动态观察钩藤对32种循环神经递质的整体作用 从时间维度来看。


In the present study, we aimed to use metabolomics platforms to examine circadian-regulated neurotransmitters across a 24-h day and the effects of Uncaria administration on daily rhythmicity in order to establish a strategy for evaluating the spatiotemporal efficacy evaluation strategy of Uncaria. By using targeted ultrahigh performance liquid chromatography-mass spectrometry metabolomics, we quantified 32 neurotransmitter metabolites every 4 h over 24 h. To assess 24-h metabolite rhythmicity, we performed cosinor analysis. The expression of hypothalamic rhythm genes was detected by reverse transcription polymerase chain reaction (RT-PCR). Data revealed circadian loss of many neurotransmitters during the entire circadian cycle in the serum of group M, indicating that hypertension causes circadian rhythm disorders. Cosinor analysis of the rhythmic oscillations of the levels of 32 neurotransmitters in the three groups showed that the metabolite rhythms peaked at approximately the same time of day (ZT4 and ZT16). Moreover, the amplitudes of the metabolite rhythms were altered. After treatment with Uncaria, the amplitudes of 13 neurotransmitters reverted to normal. The change trends in the hypothalamic rhythm genes confirmed the rhythm changes in neurotransmitters. Collectively, a novel pharmacodynamic evaluation strategy was established to dynamically observe the holistic effects of Uncaria on 32 circulating neurotransmitters within 24 h from the perspective of time dimension.

In the present study, we aimed to use metabolomics platforms to examine circadian-regulated neurotransmitters across a 24-h day and the effects of Uncaria administration on daily rhythmicity in order to establish a strategy for evaluating the spatiotemporal efficacy evaluation strategy of Uncaria. By using targeted ultrahigh performance liquid chromatography-mass spectrometry metabolomics, we quantified 32 neurotransmitter metabolites every 4 h over 24 h. To assess 24-h metabolite rhythmicity, we performed cosinor analysis. The expression of hypothalamic rhythm genes was detected by reverse transcription polymerase chain reaction (RT-PCR). Data revealed circadian loss of many neurotransmitters during the entire circadian cycle in the serum of group M, indicating that hypertension causes circadian rhythm disorders. Cosinor analysis of the rhythmic oscillations of the levels of 32 neurotransmitters in the three groups showed that the metabolite rhythms peaked at approximately the same time of day (ZT4 and ZT16). Moreover, the amplitudes of the metabolite rhythms were altered. After treatment with Uncaria, the amplitudes of 13 neurotransmitters reverted to normal. The change trends in the hypothalamic rhythm genes confirmed the rhythm changes in neurotransmitters. Collectively, a novel pharmacodynamic evaluation strategy was established to dynamically observe the holistic effects of Uncaria on 32 circulating neurotransmitters within 24 h from the perspective of time dimension.


获取全文 10.1016/j.biopha.2020.110704