Institute of Pathological Physiology of the First Faculty of Medicine, Charles University, Prague, Czech Republic.
Physiol Res. 2009;58(6):827-833. doi: 10.33549/physiolres.931678. Epub 2008 Dec 17.
Hepcidin is a key regulator of iron metabolism and a mediator of anemia in inflammation. Recent in vitro studies recognized prohepcidin as a type II acute phase protein regulating via interleukin-6. The aim of the present study was to investigate the time course of plasma prohepcidin after a large cardiac surgery in relation to IL-6 and other inflammatory parameters. Patients with chronic thromboembolic hypertension (n=22, males/females 14/8, age 51.9+/-10.2 years) underwent pulmonary endarterectomy using cardiopulmonary bypass and deep hypothermic circulatory arrest were included into study. Arterial concentrations of prohepcidin, IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and C-reactive protein were measured before/after sternotomy, after circulatory arrest, after separation from bypass, and then 12, 18, 24, 36, 48 h and 72 h after the separation from bypass. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. Pulmonary endarterectomy induced a 48% fall in plasma prohepcidin; minimal concentrations were detected after separation from cardiopulmonary bypass. Prohepcidin decline correlated with an extracorporeal circulation time (p<0.01), while elevated IL-6 levels were inversely associated with duration of prohepcidin decline. Postoperative prohepcidin did not correlate with markers of iron metabolism or hemoglobin concentrations within a 72-h period after separation from CPB. Prohepcidin showed itself as a negative acute phase reactant during systemic inflammatory response syndrome associated with a cardiac surgery. Results indicate that the evolution of prohepcidin in postoperative period implies the antagonism of stimulatory effect of IL-6 and contraregulatory factors inhibiting prohepcidin synthesis or increasing prohepcidin clearance.
亚铁调素是铁代谢的关键调节剂，也是炎症性贫血的介质。最近的体外研究发现，原亚铁调素作为一种 II 型急性时相蛋白，通过白细胞介素 6 进行调节。本研究旨在探讨大型心脏手术后血浆原亚铁调素的时间过程与白细胞介素 6 和其他炎症参数的关系。慢性血栓栓塞性高血压患者（n=22，男/女 14/8，年龄 51.9+/-10.2 岁）接受心肺旁路和深低温循环停止的肺动脉内膜切除术，纳入研究。在胸骨切开术前/后、循环停止后、旁路分离后、旁路分离后 12、18、24、36、48 和 72 小时测量动脉原亚铁调素、白细胞介素-1β、白细胞介素-6、白细胞介素-8、肿瘤坏死因子-α和 C 反应蛋白的浓度。并监测血流动力学参数、血细胞比容和铁代谢标志物。肺动脉内膜切除术导致血浆原亚铁调素下降 48%；在心肺旁路分离后检测到最低浓度。原亚铁调素的下降与体外循环时间相关（p<0.01），而白细胞介素-6 水平升高与原亚铁调素下降时间呈负相关。在心肺旁路分离后 72 小时内，术后原亚铁调素与铁代谢标志物或血红蛋白浓度无相关性。原亚铁调素在与心脏手术相关的全身炎症反应综合征中表现为负急性时相反应物。结果表明，术后原亚铁调素的演变意味着白细胞介素 6 的刺激作用与抑制原亚铁调素合成或增加原亚铁调素清除的拮抗因素之间存在拮抗作用。
