Lu Yanxia, Ho Cyrus S, Liu Xin, Chua Anna N, Wang Wei, McIntyre Roger S, Ho Roger C
Department of Clinical Psychology and Psychiatry/School of Public Health, Zhejiang University College of Medicine, Hangzhou, China.
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
PLoS One. 2017 Oct 19;12(10):e0186700. doi: 10.1371/journal.pone.0186700. eCollection 2017.
This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS) which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9), CMS+fluoxetine (n = 9) and the control (n = 6) groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (p<0.05). There was a trend of reduction of IL-6 and TNF-α concentration. This study revealed the potential therapeutic effects of fluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.
本研究评估了常用的选择性5-羟色胺再摄取抑制剂（SSRI）抗抑郁药氟西汀，在一种类似于人类抑郁体验的慢性轻度应激（CMS）大鼠模型中，对包括白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-17（IL-17）在内的炎性细胞因子外周和中枢水平的长期影响。将24只斯普拉格-道利大鼠随机分为CMS+赋形剂组（n = 9）、CMS+氟西汀组（n = 9）和对照组（n = 6）。进行蔗糖偏好试验和强迫游泳试验以评估行为变化。在第0、60、90和120天采集血样，用于测量血浆中的细胞因子水平。在第120天，取出大脑，使用Luminex检测细胞因子的中枢水平。四个月的氟西汀治疗导致蔗糖偏好和不动时间测量值发生变化，与抗抑郁作用相符。CMS+赋形剂组在第60天或120天时血浆中IL-1β、IL-17和TNF-α水平升高。分别在90天和120天治疗后，用氟西汀治疗的大鼠血浆和大脑中的IL-1β水平较低（p<0.05）。IL-6和TNF-α浓度有降低趋势。本研究揭示了氟西汀通过降低中枢和外周IL-1β水平在缓解抑郁症状方面的潜在治疗作用。
