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使用血清、血浆和血小板5-羟色胺作为抑郁症诊断及抗抑郁药反应评估的外周生物标志物的可行性:动物实验研究

Feasibility of Using Serum, Plasma, and Platelet 5-hydroxytryptamine as Peripheral Biomarker for the Depression Diagnosis and Response Evaluation to Antidepressants: Animal Experimental Study.

作者信息

Su Zuanjun, Chen Zhicong, Cao Jinming, Li Canye, Duan Jingjing, Zhou Ting, Yang Zhen, Cheng Yuanchi, Xiao Zhijun, Xu Feng

机构信息

Department of Clinical Pharmacy, Fengxian Hospital and School of Pharmaceutical Science, Southern Medical University, Shanghai, China.

Department of Pharmacology, Sixth People's Hospital South Campus, Shanghai Jiaotong University, Shanghai, China.

出版信息

Clin Psychopharmacol Neurosci. 2024 Nov 30;22(4):594-609. doi: 10.9758/cpn.24.1167. Epub 2024 May 3.

Abstract

OBJECTIVE

Whether peripheral blood 5-hydroxytrptamine (5-HT) levels serve as biomarker for depression diagnosis/response evaluation has not been well determined. This work was explored to address this inconclusive issue.

METHODS

Animals were randomized into normal control group (NC, n = 10) and chronic unpredictable mild stress model group (CUMS-model, n = 20), respectively. Animals in CUMS-model group were subjected to chronic stress, then they were randomly subdivided into CUMS subgroup and CUMS + fluoxetine subgroup (CUMS + FLX). After FLX treatment, blood and tissues were collected. 5-HT and relevant protein expression were measured.

RESULTS

In mice model, there was a significant increase in serum and a significant reduction in plasma 5-HT levels in CUMS-model group versus NC group, while platelet 5-HT levels change little. After FLX treatment, serum and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup, while plasma 5-HT levels had not much change versus CUMS subgroup. Chronic stress enhanced colon and platelet serotonin transporter (SERT) expression and FLX treatment mitigated SERT expression. In rats' model, there was a significant increase in serum 5-HT levels while plasma and platelet 5-HT levels showed little change in CUMS group versus NC group. After FLX treatment, serum, plasma and platelet 5-HT levels were significantly decreased in CUMS + FLX subgroup versus CUMS subgroup. The profile of relevant proteins expression changed by FLX were like those in mice.

CONCLUSION

Serum 5-HT levels might serve as a potential biomarker for depression diagnosis, meanwhile serum and platelet 5-HT levels might respond to antidepressant treatment.

摘要

目的

外周血5-羟色胺(5-HT)水平是否可作为抑郁症诊断/反应评估的生物标志物尚未明确。本研究旨在探讨这一尚无定论的问题。

方法

将动物随机分为正常对照组(NC,n = 10)和慢性不可预测轻度应激模型组(CUMS模型组,n = 20)。对CUMS模型组动物施加慢性应激,然后将其随机分为CUMS亚组和CUMS + 氟西汀亚组(CUMS + FLX)。FLX治疗后,采集血液和组织。检测5-HT及相关蛋白表达。

结果

在小鼠模型中,与NC组相比,CUMS模型组血清5-HT水平显著升高,血浆5-HT水平显著降低,而血小板5-HT水平变化不大。FLX治疗后,CUMS + FLX亚组血清和血小板5-HT水平显著降低,而与CUMS亚组相比,血浆5-HT水平变化不大。慢性应激增强了结肠和血小板5-羟色胺转运体(SERT)的表达,FLX治疗减轻了SERT的表达。在大鼠模型中,与NC组相比,CUMS组血清5-HT水平显著升高,而血浆和血小板5-HT水平变化不大。FLX治疗后,与CUMS亚组相比,CUMS + FLX亚组血清、血浆和血小板5-HT水平显著降低。FLX引起的相关蛋白表达变化情况与小鼠相似。

结论

血清5-HT水平可能作为抑郁症诊断的潜在生物标志物,同时血清和血小板5-HT水平可能对抗抑郁治疗有反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11494436/9b423716679d/cpn-22-4-594-f1.jpg

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