Demirtaş Tuğçe, Utkan Tijen, Karson Ayşe, Yazır Yusufhan, Bayramgürler Dilek, Gacar Nejat
Department of Pharmacology, Medical Faculty, Kocaeli University, Medical Faculty, 41380, Kocaeli, Turkey,
Inflammation. 2014 Oct;37(5):1432-8. doi: 10.1007/s10753-014-9867-4.
Inflammation has been suggested to be associated with stress-induced depression and cardiovascular dysfunction. Tumor necrosis factor alpha (TNF-α) is a major cytokine in the activation of neuroendocrine, immune, and behavioral responses. In this study, we investigated the effects of infliximab (a TNF-α inhibitor) on endothelium-dependent vascular reactivity, systemic blood pressure, and endothelial nitric oxide synthase (eNOS) immunoreactivity in the unpredictable chronic mild stress (UCMS) model of depression in rats. There was no significant change between all groups in the systemic blood pressure. In UCMS, endothelium-dependent relaxation of the smooth muscle in response to carbachol was significantly decreased with 50 % maximal response (E max) and pD2 values compared with the controls. Infliximab was able to reverse this UCMS effect. Relaxation in response to the nitric oxide (NO) donor sodium nitroprusside and papaverine and KCl-induced contractile responses was similar between groups. In UCMS, decreased expression of eNOS was detected. Moreover, there was no significant change in UCMS + infliximab group with respect to control rats. Our results suggest that tumor necrosis factor-alpha (TNF-α) could be a major mediator of vascular dysfunction associated with UCMS, leading to decreased expression of eNOS.
炎症被认为与应激诱导的抑郁和心血管功能障碍有关。肿瘤坏死因子α（TNF-α）是激活神经内分泌、免疫和行为反应的主要细胞因子。在本研究中，我们在大鼠不可预测的慢性轻度应激（UCMS）抑郁模型中，研究了英夫利昔单抗（一种TNF-α抑制剂）对内皮依赖性血管反应性、全身血压和内皮型一氧化氮合酶（eNOS）免疫反应性的影响。所有组之间的全身血压没有显著变化。在UCMS中，与对照组相比，对卡巴胆碱反应的平滑肌内皮依赖性舒张以最大反应的50%（E max）和pD2值显著降低。英夫利昔单抗能够逆转这种UCMS效应。各组对一氧化氮（NO）供体硝普钠和罂粟碱的舒张反应以及KCl诱导的收缩反应相似。在UCMS中，检测到eNOS表达降低。此外，UCMS + 英夫利昔单抗组与对照大鼠相比没有显著变化。我们的结果表明，肿瘤坏死因子-α（TNF-α）可能是与UCMS相关的血管功能障碍的主要介质，导致eNOS表达降低。
