Department of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Pediatr Crit Care Med. 2012 Sep;13(5):e323-9. doi: 10.1097/PCC.0b013e31824fbd90.
We previously demonstrated that altered zinc homeostasis is an important feature of pediatric sepsis, thus raising the possibility of zinc supplementation as a therapeutic strategy in sepsis. Herein, we tested the hypothesis that prophylactic zinc supplementation would be beneficial in a murine model of peritoneal sepsis.
Murine model of sepsis (intraperitoneal fecal-slurry injection).
Basic science research laboratory.
C57BL/6 male mice.
Intraperitoneal fecal-slurry injection, with or without zinc supplementation (10 mg/kg of intraperitoneal zinc gluconate for 3 days prior to intraperitoneal fecal-slurry injection).
Survival over 3 days following intraperitoneal fecal-slurry injection, markers of inflammation, bacterial load studies, and immunophenotyping studies. Zinc-supplemented mice demonstrated a significant survival advantage compared to control (nonsupplemented) mice. Zinc-supplemented mice also demonstrated moderate reductions of inflammation and immune activation. The survival advantage primarily correlated with reduced in vivo bacterial load in zinc-supplemented mice, compared to controls. In addition, peritoneal macrophages harvested from zinc-supplemented mice demonstrated a significantly enhanced phagocytosis capacity for Escherichia coli and Staphylococcus aureus, compared to peritoneal macrophages harvested from control mice.
Prophylactic zinc supplementation reduces bacterial load and is beneficial in a murine model of peritoneal sepsis.
我们之前的研究表明，锌稳态的改变是小儿败血症的一个重要特征，因此补锌可能成为败血症的一种治疗策略。在此，我们通过腹腔脓毒症模型来验证预防性补锌是否有益的假设。
脓毒症的小鼠模型（腹腔粪便混悬液注射）。
基础科学研究实验室。
C57BL/6 雄性小鼠。
腹腔粪便混悬液注射，补锌或不补锌（腹腔注射锌葡萄糖酸 10mg/kg，连续 3 天）。
腹腔粪便混悬液注射后 3 天的存活情况、炎症标志物、细菌负荷研究和免疫表型研究。与对照组（未补锌）相比，补锌组小鼠的存活率有显著提高。补锌组还表现出炎症和免疫激活的适度减轻。与对照组相比，补锌组小鼠体内细菌负荷的减少与存活率的提高密切相关。此外，与对照组小鼠来源的腹腔巨噬细胞相比，从补锌组小鼠中分离出的腹腔巨噬细胞对大肠杆菌和金黄色葡萄球菌的吞噬能力显著增强。
预防性补锌可降低细菌负荷，对腹腔脓毒症的小鼠模型有益。
