Huber Nathan L, Bailey Stephanie R, Schuster Rebecca, Ogle Cora K, Lentsch Alex B, Pritts Timothy A
Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0558, USA.
J Burn Care Res. 2012 Mar-Apr;33(2):279-85. doi: 10.1097/BCR.0b013e3182331d75.
The objective of this study was to increase the understanding of the "second-hit" response in thermal injury. The authors hypothesized that prior thermal injury increases the endotoxin-induced inflammatory response of intestinal mucosa. Mice underwent sham or 25% TBSA scald injury. Seven days after injury, mice were injected with lipopolysaccharide. Blood, jejunum, and colon specimens were obtained at intervals. Serum, jejunal, and colon inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. Jejunal and colon nuclear factor (NF)-κB activation was measured by electrophoretic mobility shift assay. After remote thermal injury, lipopolysaccharide exposure led to an acute increase in serum interleukin (IL)-6, IL-10, and chemokine keratinocyte-derived chemokine (KC) levels. This correlated with lipopolysaccharide-induced increased IL-6 in colon and chemokine KC in the jejunum and colon in burned mice when compared with sham-injured mice. Lipopolysaccharide-induced NF-κB activation occurred more rapidly in jejunum and colon from burned mice compared with sham-injured mice. Prior thermal injury accelerates lipopolysaccharide-induced inflammatory cytokine production systemically in jejunum and colon. The "second hit" of lipopolysaccharide led to earlier intestinal NF-κB activation in burned mice compared with sham-injured mice. These results indicate that there is a heightened inflammatory response by jejunum and colon in response to a "second hit" of lipopolysaccharide after burn injury.
本研究的目的是增进对热损伤中“二次打击”反应的理解。作者推测，先前的热损伤会增加内毒素诱导的肠黏膜炎症反应。小鼠接受假手术或25%体表面积的烫伤。损伤后7天，给小鼠注射脂多糖。每隔一段时间采集血液、空肠和结肠标本。通过酶联免疫吸附测定法测量血清、空肠和结肠炎症细胞因子水平。通过电泳迁移率变动分析测量空肠和结肠核因子（NF）-κB的激活情况。在远程热损伤后，脂多糖暴露导致血清白细胞介素（IL）-6、IL-10和趋化因子角质形成细胞衍生趋化因子（KC）水平急性升高。与假手术损伤小鼠相比，这与脂多糖诱导的烧伤小鼠结肠中IL-6增加以及空肠和结肠中趋化因子KC增加相关。与假手术损伤小鼠相比，脂多糖诱导的NF-κB激活在烧伤小鼠的空肠和结肠中发生得更快。先前的热损伤会加速脂多糖诱导的空肠和结肠系统性炎症细胞因子的产生。与假手术损伤小鼠相比，脂多糖的“二次打击”导致烧伤小鼠肠道NF-κB激活更早。这些结果表明，烧伤后空肠和结肠对脂多糖的“二次打击”有增强的炎症反应。
