Department of Biology, Western Kentucky University, Bowling Green, Kentucky.
Department of Pharmacology, University of Kentucky, Lexington, Kentucky.
Am J Physiol Regul Integr Comp Physiol. 2020 Apr 1;318(4):R781-R789. doi: 10.1152/ajpregu.00358.2019. Epub 2020 Mar 4.
Sleep loss contributes to the development of cardiovascular, metabolic, and neurological disorders by promoting a systemic proinflammatory phenotype. The neuroendocrine-immune mechanisms contributing to such pathologies are poorly understood. The sympathetic nervous system (SNS) regulates immunity and is often activated following sleep disturbances. The aims of this study were to determine ) the effect of SNS inhibition on inflammatory responses to sleep fragmentation (SF) and ) whether homeostasis can be restored after 1 wk of recovery sleep. We measured stress responses (norepinephrine and corticosterone), gene expression levels of pro- and anti-inflammatory cytokines in peripheral (heart, liver, and spleen) tissues, and protein levels of cytokines and chemokines in serum of female mice that were subjected to acute SF for 24 h, chronic SF for 8 wk, or 7 days of recovery after chronic SF. In each experiment, SF and control mice were chemically sympathectomized with 6-hydroxydopamine (6-OHDA) or injected with vehicle. Both acute and chronic SF elevated mRNA and protein levels of cytokines in peripheral tissues. Changes in inflammatory responses mirrored stress-axes activation, with increased corticosterone and norepinephrine in SF mice. 6-OHDA treatment significantly alleviated SF-induced inflammation, thus providing evidence of SNS regulation of peripheral inflammation from SF. Effects of chronic SF were more severe than acute SF, and 1 wk of recovery from SF sufficiently alleviated peripheral inflammatory responses but not NE responses.
睡眠缺失通过促进全身性促炎表型而导致心血管、代谢和神经紊乱的发展。促成这些病理的神经内分泌-免疫机制仍了解甚少。交感神经系统（SNS）调节免疫，并且常因睡眠障碍而被激活。本研究的目的是确定：）SNS 抑制对睡眠碎片化（SF）引起的炎症反应的影响，以及）在恢复睡眠 1 周后，是否可以恢复体内平衡。我们测量了应激反应（去甲肾上腺素和皮质酮）、外周（心脏、肝脏和脾脏）组织中促炎和抗炎细胞因子的基因表达水平，以及经历了 24 小时急性 SF、8 周慢性 SF 或慢性 SF 后 7 天恢复的雌性小鼠血清中细胞因子和趋化因子的蛋白水平。在每个实验中，SF 和对照小鼠均用 6-羟多巴胺（6-OHDA）进行化学交感神经切除术或注射载体。急性和慢性 SF 均增加了外周组织中细胞因子的 mRNA 和蛋白水平。炎症反应的变化反映了应激轴的激活，SF 小鼠的皮质酮和去甲肾上腺素增加。6-OHDA 处理显著缓解了 SF 引起的炎症，从而提供了 SNS 调节 SF 引起的外周炎症的证据。慢性 SF 的影响比急性 SF 更严重，SF 恢复 1 周足以缓解外周炎症反应，但不能缓解 NE 反应。
