PDF(Pubmed)
Abstract：
Chronic psychological stress has been reported to decrease circulating iron concentrations and impair hematopoiesis. However, the underlying mechanisms remain unclear. This study aimed to investigate the effects of psychological stress on biological iron metabolism by using the social defeat stress (SDS) model, a widely used model of depression. Compared with control mice, mice subjected to SDS (SDS mice) had lower social interaction (SI) behavior. The SDS mice also showed impaired hematopoiesis, as evidenced by reduced circulating red blood cell counts, elevated reticulocyte counts, and decreased plasma iron levels. In the SDS mice, the iron contents in the bone marrow decreased, whereas those in the spleen increased, suggesting dysregulation in systemic iron metabolism. The concentrations of plasma hepcidin, an important regulator of systemic iron homeostasis, increased in the SDS mice. Meanwhile, the concentrations of ferroportin, an iron transport protein negatively regulated by hepcidin, were lower in the spleen and duodenum of the SDS mice than in those of the control mice. Treatment with dalteparin, a hepcidin inhibitor, prevented the decrease in plasma iron levels in the SDS mice. The gene expression and enzyme activity of furin, which converts the precursor hepcidin to active hepcidin, were high and positively correlated with plasma hepcidin concentration. Thus, furin activation might be responsible for the increased plasma hepcidin concentration. This study is the first to show that psychological stress disrupts systemic iron homeostasis by activating the hepcidin-ferroportin axis. Consideration of psychological stressors might be beneficial in the treatment of diseases with iron-refractory anemia.
摘要：
据报道，慢性心理压力会降低循环铁浓度并损害造血功能。然而,潜在机制尚不清楚.本研究采用社会失败应激(SDS)模型,探讨心理应激对生物铁代谢的影响。广泛使用的抑郁症模型。与对照小鼠相比，接受SDS的小鼠（SDS小鼠）具有较低的社交互动（SI）行为。SDS小鼠还表现出造血功能受损，循环红细胞计数减少证明了这一点，网织红细胞计数升高,和降低血浆铁水平。在SDS小鼠中，骨髓中的铁含量下降，而脾脏中的增加，提示全身铁代谢失调。血浆铁调素的浓度，系统铁稳态的重要调节剂，在SDS小鼠中增加。同时,运铁素的浓度，铁调素负调控的铁转运蛋白，SDS小鼠的脾脏和十二指肠低于对照小鼠。用达肝素治疗，铁调素抑制剂,防止SDS小鼠血浆铁水平的降低。弗林蛋白酶的基因表达和酶活性，将前体铁调素转化为活性铁调素，与血浆铁调素浓度呈正相关。因此，弗林蛋白酶的激活可能是导致血浆铁调素浓度升高的原因。这项研究首次表明心理压力通过激活铁调素-铁转运蛋白轴来破坏全身铁稳态。考虑心理压力源可能对治疗铁难治性贫血的疾病有益。
