期刊
CRITICAL CARE MEDICINE
卷 41, 期 4, 页码 1075-1085出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0b013e318275d1f9
关键词
femur fracture; gene expression; hemorrhage; immune suppression; inflammation; trauma
资金
- National Institute of General Medical Sciences (NIGMS) [R01 GM040586-21S1, R01 GM081923-05]
- NIGMS [T32 GM008721-12]
- University of Florida
Objective: To develop a novel polytrauma model that better recapitulates the immunologic response of the severely injured patient by combining long-bone fracture, muscle tissue damage, and cecectomy with hemorrhagic shock, resulting in an equivalent Injury Severity Score of greater than 15. We compared this new polytrauma/shock model to historically used murine trauma-hemorrhage models. Design: Pre-clinical controlled in vivo laboratory study. Setting: Laboratory of Inflammation Biology and Surgical Science. Subjects: Six-to 10-week-old C57BL/6 (B6) mice. Interventions: Mice underwent 90 minutes of shock (mean arterial pressure 30 mm Hg) and resuscitation via femoral artery cannulation followed by laparotomy (trauma-hemorrhage), hemorrhage with laparotomy and femur fracture, or laparotomy with cecetomy and femur fracture with muscle tissue damage (polytrauma). Mice were euthanized at 2 hours, 1 day, and 3 days postinjury. Measurements and Main Results: The spleen, bone marrow, blood, and serum were collected from mice for analysis at the above time points. None of the models were lethal. Mice undergoing polytrauma exhibited a more robust inflammatory response with significant elevations in cytokine/chemokine concentrations when compared with traditional models. Polytrauma was the only model to induce neutrophilia (Ly6G(+)CD11b(+) cells) on days 1 and 3 (p < 0.05). Polytrauma, as compared to trauma-hemorrhage and hemorrhage with laparotomy and femur fracture, induced a loss of circulating CD4(+) T cell with simultaneous increased cell activation (CD69(+) and CD25(+)), similar to human trauma. There was a prolonged loss of major histocompatibility complex class II expression on monocytes in the polytrauma model (p < 0.05). Results were confirmed by genome-wide expression analysis that revealed a greater magnitude and duration of blood leukocyte gene expression changes in the polytrauma model than the trauma-hemorrhage and sham models. Conclusions: This novel polytrauma model better replicates the human leukocyte, cytokine, and overall inflammatory response following injury and hemorrhagic shock. (Crit Care Med 2013; 41:1075-1085)
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