Crowell Kristen T, Phillips Brett E, Kelleher Shannon L, Soybel David I, Lang Charles H
Department of Surgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
Department of Surgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania.
J Surg Res. 2017 Apr;210:47-58. doi: 10.1016/j.jss.2016.10.020. Epub 2016 Nov 2.
Mild dietary zinc (Zn) deficiency is widespread in human populations, but its influence on recovery after acute illness is poorly understood. In a mouse model of abdominal sepsis (cecal ligation puncture), systemic immune responses and liver metabolism were monitored in early (24 h) and late (5 d) phases, under control conditions and during mild dietary Zn restriction.
Mice were fed diets adequate or marginally deficient (ZM) in Zn (30 versus 10 mg zinc/kg diet) for 4 wk, before undergoing laparotomy alone (nonseptic control) or cecal ligation puncture (septic).
Among nonseptic mice, the ZM state was not associated with differences in inflammation or metabolic responses. Among septic mice, mortality did not differ between the zinc adequate and ZM groups. In the early phase, the ZM state amplified increases in plasma interleukin (IL) 6, tumor necrosis factor alpha, and IL-10, while dampening the interferon gamma response. In the late phase, subtle but significant ZM-associated increases were observed in plasma IL-5 and interferon gamma levels and hepatic protein synthesis, the latter of which appeared to be mammalian target of rapamycin independent and was associated with increased hepatic tumor necrosis factor alpha messenger RNA content.
Without increasing mortality, the ZM state is associated with a more disordered acute systemic inflammatory response and persistence or enhancement of acute phase responses within the liver parenchyma.
轻度膳食锌缺乏在人群中普遍存在，但对急性疾病后恢复的影响却知之甚少。在腹部脓毒症（盲肠结扎穿刺）小鼠模型中，在对照条件下以及轻度膳食锌限制期间，于早期（24小时）和晚期（5天）监测全身免疫反应和肝脏代谢。
小鼠先喂食锌含量充足或轻度缺乏（ZM）的饲料（分别为每千克饲料含锌30毫克和10毫克）4周，然后单独进行剖腹手术（非脓毒症对照）或盲肠结扎穿刺（脓毒症）。
在非脓毒症小鼠中，ZM状态与炎症或代谢反应的差异无关。在脓毒症小鼠中，锌充足组和ZM组的死亡率没有差异。在早期，ZM状态放大了血浆白细胞介素（IL）-6、肿瘤坏死因子α和IL-10的升高，同时抑制了干扰素γ反应。在晚期，观察到血浆IL-5和干扰素γ水平以及肝脏蛋白质合成出现与ZM相关的细微但显著的升高，后者似乎独立于雷帕霉素的哺乳动物靶点，并且与肝脏肿瘤坏死因子α信使核糖核酸含量增加有关。
在不增加死亡率的情况下，ZM状态与更紊乱的急性全身炎症反应以及肝实质内急性期反应的持续或增强有关。
