Shi Wen-Lei, Zhang Ting, Zhou Jiang-Rui, Huang Yong-Hua, Jiang Chun-Lei
Department of Neurology, General Army Hospital, Beijing 10070, China; Department of Neurology, Bethune International Peace Hospital, Shijiazhuang, Hebei 050082, China; Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China.
Department of Naval Aviation Medicine, Second Military Medical University (SMMU), Shanghai 200433, China.
Biomed Pharmacother. 2016 Dec;84:1119-1125. doi: 10.1016/j.biopha.2016.10.029. Epub 2016 Oct 22.
Glucocorticoids (GCs) play a vital role in the regulation of blood pressure by their permissive effects in potentiating vasoactive responses to catecholamines through glucocorticoid receptors. GCs achieve this function by controlling vascular smooth muscle tone. Clinically, low to moderate doses of GCs are generally used in the treatment of septic shock in recent years. GCs are now known to have both genomic and non-genomic effects. While genomic effects of GCs were well studied, few non-genomic effects were reported, much less the non-genomic mechanisms. One of the most important characters of their non-genomic effects is short latency. The aim of this study was to determine whether GCs can rapidly regulate blood pressure by their permissive action on norepinephrine (NE). Adrenalectomized rats were subjected to cecal ligation and puncture to induce septic shock. The septic rats displayed a significant decrease in the blood pressure response to NE. Dexamethasone (DEX) rapidly restores this hyporeactivity to NE in adrenalectomized septic rats. Further studies showed that DEX potentiates the NE-induced shrinkage and actin cytoskeleton rearrangement of single cell from mesenteric arteries in a short time. These findings suggest that GCs probably exert their permissive actions on the pressure response to NE through rapid non-genomic mechanisms. In this article, we found that as an adjunctive therapy for septic shock, the use of GCs may involve a rapid permissive action, and non-genomic effects of GCs may be involved in these processes.
糖皮质激素（GCs）通过糖皮质激素受体增强对儿茶酚胺的血管活性反应，发挥其在血压调节中的重要作用。GCs通过控制血管平滑肌张力来实现这一功能。近年来，临床治疗感染性休克时通常使用低至中等剂量的GCs。目前已知GCs具有基因组效应和非基因组效应。虽然GCs的基因组效应已得到充分研究，但关于非基因组效应的报道较少，非基因组机制的报道则更少。其非基因组效应的一个最重要特点是潜伏期短。本研究的目的是确定GCs是否能通过其对去甲肾上腺素（NE）的允许作用快速调节血压。对肾上腺切除的大鼠进行盲肠结扎和穿刺以诱导感染性休克。感染性休克大鼠对NE的血压反应显著降低。地塞米松（DEX）能迅速恢复肾上腺切除的感染性休克大鼠对NE的这种低反应性。进一步研究表明，DEX能在短时间内增强NE诱导的肠系膜动脉单细胞收缩和肌动蛋白细胞骨架重排。这些发现提示，GCs可能通过快速的非基因组机制对NE的压力反应发挥其允许作用。在本文中，我们发现，作为感染性休克的辅助治疗，GCs的使用可能涉及快速的允许作用，且GCs的非基因组效应可能参与这些过程。
