Kocaeli University Center for Stem Cell and Gene Therapies Research and Practice, Institute of Health Sciences, Kocaeli, Turkey.
Kocaeli University Faculty of Medicine, Department of Pharmacology, Kocaeli, Turkey.
Behav Brain Res. 2023 Feb 13;438:114186. doi: 10.1016/j.bbr.2022.114186. Epub 2022 Nov 4.
Chronic psychological stress may cause depression and it is a risk factor for vascular endothelial dysfunction. Inflammation may contribute to endothelial dysfunction. Resveratrol, which has antiinflammatory and vasculoprotective properties, has been reported its beneficial effects on endothelial dysfunction induced by hypertension, diabetes and, aging. The effects of resveratrol on stress-induced endothelial dysfunction is not investigated yet. This study aimed to investigate the efficacy of resveratrol on vascular function in the unpredictable chronic moderate stress (UCMS) model of rats and to examine the possible mechanisms of resveratrol by assessment of proinflammatory markers. Male rats were assigned to 4 groups (n = 8 for each group): Control, Control+Resveratrol, UCMS, UCMS+Resveratrol. UCMS and UCMS+Resveratrol groups were exposed to the UCMS procedure for 12 weeks. Resveratrol (20 mg/kg/day, i.p., during 12 weeks) was given to the Control+Resveratrol and UCMS+Resveratrol groups.Then depressive-like behaviors were evaluated by forced swimming test. After behavioral tests, systolic blood pressure was recorded. Endothelial function of the thoracic aorta was evaluated by isolated organ bath system. Vascular eNOS expression and inflammatory markers such as TNF-α, IL-1β, IL-6, CRP, ICAM1, MCP in serum and vascular tissue were analyzed to explore the mechanisms of resveratrol. UCMS resulted in depressive-like behavior, endothelial dysfunction and increased inflammatory cytokines in both serum and tissue samples. Resveratrol treatment improved depressive-like behavior, ameliorated vascular dysfunction, and reversed stress-induced inflammation. Our findings suggest that resveratrol exerted antidepressant-like effect and prevented vascular endothelial dysfunction by reducing systemic and peripheral inflammation in UCMS-induced depression in rats. Therefore, resveratrol may be a therapeutic option with a vasculoprotective effect in depression.
慢性心理应激可导致抑郁，是血管内皮功能障碍的危险因素。炎症可能导致内皮功能障碍。白藜芦醇具有抗炎和血管保护作用，据报道其对高血压、糖尿病和衰老引起的内皮功能障碍有有益作用。然而，白藜芦醇对应激引起的内皮功能障碍的影响尚未得到研究。本研究旨在探讨白藜芦醇对大鼠不可预测慢性中度应激（UCMS）模型血管功能的影响，并通过评估促炎标志物来研究白藜芦醇的可能机制。雄性大鼠分为 4 组（每组 8 只）：对照组、对照组+白藜芦醇组、UCMS 组、UCMS+白藜芦醇组。UCMS 组和 UCMS+白藜芦醇组接受 UCMS 程序 12 周。在 12 周期间，给予对照组+白藜芦醇组和 UCMS+白藜芦醇组白藜芦醇（20mg/kg/天，腹腔注射）。然后通过强迫游泳试验评估抑郁样行为。行为测试后，记录收缩压。采用离体器官浴系统评估胸主动脉内皮功能。分析血清和血管组织中血管 eNOS 表达和炎症标志物，如 TNF-α、IL-1β、IL-6、CRP、ICAM1、MCP，以探讨白藜芦醇的作用机制。UCMS 导致抑郁样行为、内皮功能障碍和血清和组织样本中促炎细胞因子增加。白藜芦醇治疗改善了抑郁样行为，改善了血管功能障碍，并逆转了应激引起的炎症。我们的研究结果表明，白藜芦醇通过减轻 UCMS 诱导的抑郁大鼠的全身和外周炎症，发挥抗抑郁样作用并预防血管内皮功能障碍。因此，白藜芦醇可能是一种具有血管保护作用的治疗选择。
