Wu Liyan, Yuan Zhenyan, Wang Min, Fu Xiaomeng, Liu Xiaohui, Wei Bing, Liu Yugeng
Department of Infectious Diseases and Clinical Microbiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People's Republic of China.
Emergency Medicine Clinical Research Center, Beijing Chaoyang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Clinical Center for Medicine in Acute Infection, Capital Medical University, Beijing, 100043, People's Republic of China.
Infect Drug Resist. 2024 Nov 11;17:5027-5036. doi: 10.2147/IDR.S484103. eCollection 2024.
Sepsis is a life-threatening condition associated with acute organ dysfunction. Iron is an essential trace element for multicellular organisms and almost all microorganisms, and its role in sepsis has been increasingly recognized. The aim of this study was to investigate the changes in iron metabolism in caecal ligation and puncture solution (CLP) -induced septic mice and the effects of hepcidin pretreatment on serum inflammatory marker levels and liver iron metabolism in CLP-induced septic mice.
C57BL/6 mice were given normal saline, CLP (peritonitis model) or 100 μg of hepcidin via intraperitoneal injection. The experimental animals were divided into 4 groups: the control group, model group (CLP), hepcidin pretreatment Groups CLP+hepcidin-2h and CLP+hepcidin-24 h. Blood samples were collected at 6, 12 and 24 hours after CLP surgery, and the mice were euthanized and livers were obtained.
ELISA revealed that hepcidin pretreatment, especially 2 hours in advance (p<0.01), increased the serum hepcidin, TNF-a and IL-6 in CLP-induced septic mice; the serum iron content of CLP-related septic mice decreased (P<0.01), while the liver iron content increased (P<0.01); Hepcidin pretreatment reduced the serum iron (P<0.05) at 6 h and 12 h and liver iron concentrations (P<0.01) at 6 h, 12 h and 24 h in CLP-related septic mice. Western blotting revealed that the hepatic iron absorption-related proteins transferrin receptor-2 (TFR2), ZRT/IRT-like protein 14 (ZIP14) and divalent meta lion transporter-1 (DMT1) were elevated (P<0.01); The iron-exporting protein ferroportin (SLC40A1) was decreased (P<0.01) throughout CLP and CLP+hepcidin sepsis. Compared with CLP group, the protein expressions in the CLP+ hepcidin-2 h group were more obvious than that in the CLP+ hepcidin-24 h group.
Hepcidin has proinflammatory effect. Hepcidin exacerbates iron metabolism imbalances in sepsis by influencing the expression of iron absorption-related proteins and iron export-related proteins.
脓毒症是一种与急性器官功能障碍相关的危及生命的病症。铁是多细胞生物和几乎所有微生物必需的微量元素，其在脓毒症中的作用已得到越来越多的认识。本研究的目的是探讨盲肠结扎和穿刺溶液（CLP）诱导的脓毒症小鼠铁代谢的变化以及铁调素预处理对CLP诱导的脓毒症小鼠血清炎症标志物水平和肝脏铁代谢的影响。
通过腹腔注射给予C57BL/6小鼠生理盐水、CLP（腹膜炎模型）或100μg铁调素。将实验动物分为4组：对照组、模型组（CLP）、铁调素预处理组CLP+铁调素-2h和CLP+铁调素-24h。在CLP手术后6、12和24小时采集血样，对小鼠实施安乐死并获取肝脏。
ELISA显示，铁调素预处理，尤其是提前2小时（p<0.01），可增加CLP诱导的脓毒症小鼠血清铁调素、TNF-a和IL-6；CLP相关脓毒症小鼠血清铁含量降低（P<0.01），而肝脏铁含量增加（P<0.01）；铁调素预处理降低了CLP相关脓毒症小鼠6小时和12小时的血清铁（P<0.05）以及6小时、12小时和24小时的肝脏铁浓度（P<0.01）。蛋白质印迹法显示，肝脏铁吸收相关蛋白转铁蛋白受体-2（TFR2）、ZRT/IRT样蛋白14（ZIP14）和二价金属离子转运体-1（DMT1）升高（P<0.01）；在整个CLP和CLP+铁调素脓毒症过程中，铁输出蛋白铁转运蛋白（SLC40A1）降低（P<0.01）。与CLP组相比，CLP+铁调素-2h组的蛋白表达比CLP+铁调素-24h组更明显。
铁调素有促炎作用。铁调素通过影响铁吸收相关蛋白和铁输出相关蛋白的表达，加剧脓毒症中铁代谢失衡。
