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帕罗西汀治疗抑郁状态下血浆一碳代谢因子分布及氨基酸谱:一项模型研究。

Distribution of Plasma One-Carbon Metabolism Factors and Amino Acids Profile in Depression State Treated with Paroxetine: A Model Study.

作者信息

Aghajani Reyhaneh, Naderi Nushin, Sadeghi Niloofar, Ani Mohsen, Ani Sima, Nasr-Esfahani Mohammad Hossein

机构信息

Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Department of Biochemistry and Functional Genomics, University de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.

出版信息

Cell J. 2023 Mar 7;25(3):165-175. doi: 10.22074/cellj.2023.557498.1056.

Abstract

OBJECTIVE

Stress may have an important role in the origin and progress of depression and can impair metabolic homeostasis. The one-carbon cycle (1-CC) metabolism and amino acid (AA) profile are some of the consequences related to stress. In this study, we investigated the Paroxetine treatment effect on the plasma metabolite alterations induced by forced swim stress-induced depression in mice.

MATERIALS AND METHODS

In this experimental study that was carried out in 2021, thirty male NMRI mice (6-8 weeks age, 30 ± 5 g) were divided into five groups: control, sham, paroxetine treatment only (7 mg/kg BW/day), depression induction, and Paroxetine+depression. Mice were subjected to a forced swim test (FST) to induce depression and then were treated with Paroxetine, for 35 consecutive days. The swimming and immobility times were recorded during the interventions. Then, animals were sacrificed, plasma was prepared and the concentration of 1-CC factors and twenty AAs was measured by spectrophotometry and high-performance liquid chromatography system (HPLC) techniques. Data were analyzed by SPSS, using One-Way ANOVA and Pearson Correlation, and P<0.05 was considered significant.

RESULTS

Plasma concentrations of phenylalanine, glutamate, aspartate, arginine, ornithine, citrulline, threonine, histidine, and alanine were significantly reduced in the depression group in comparison with the control group. The Homocysteine (Hcy) plasma level was increased in the Paroxetine group which can be associated with hyperhomocysteinemia. Moreover, vitamin B12, phenylalanine, glutamate, ornithine, citrulline, and glycine plasma levels were significantly reduced in the depression group after Paroxetine treatment.

CONCLUSION

This study has demonstrated an impairment in the plasma metabolites' homeostasis in depression and normal conditions after Paroxetine treatment, although, further studies are required.

摘要

目的

应激可能在抑郁症的发生和发展中起重要作用,并可能损害代谢稳态。一碳循环(1-CC)代谢和氨基酸(AA)谱是与应激相关的一些后果。在本研究中,我们调查了帕罗西汀对强迫游泳应激诱导的小鼠抑郁所引起的血浆代谢物变化的治疗效果。

材料与方法

在这项于2021年进行的实验研究中,30只雄性NMRI小鼠(6-8周龄,30±5克)被分为五组:对照组、假手术组、仅帕罗西汀治疗组(7毫克/千克体重/天)、抑郁诱导组和帕罗西汀+抑郁组。对小鼠进行强迫游泳试验(FST)以诱导抑郁,然后连续35天用帕罗西汀治疗。在干预期间记录游泳和不动时间。然后,处死动物,制备血浆,并通过分光光度法和高效液相色谱系统(HPLC)技术测量1-CC因子和20种氨基酸的浓度。数据采用SPSS进行分析,使用单因素方差分析和Pearson相关性分析,P<0.05被认为具有统计学意义。

结果

与对照组相比,抑郁组血浆中苯丙氨酸、谷氨酸、天冬氨酸、精氨酸、鸟氨酸、瓜氨酸、苏氨酸、组氨酸和丙氨酸的浓度显著降低。帕罗西汀组血浆同型半胱氨酸(Hcy)水平升高,这可能与高同型半胱氨酸血症有关。此外,帕罗西汀治疗后,抑郁组血浆维生素B12、苯丙氨酸、谷氨酸、鸟氨酸、瓜氨酸和甘氨酸水平显著降低。

结论

本研究表明,抑郁症患者以及帕罗西汀治疗后的正常情况下,血浆代谢物稳态均受到损害,不过仍需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6664/10105297/d987d98c5868/Cell-J-25-165-g01.jpg

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