创伤后内毒素血症与脏器损害关系及其防治新方法的系列研究

目的：从不同的作用环节采用多种干预手段以阻断肠源性内毒素血症的发生，观察其对机体炎症反应、免疫反应、脏器损害和预后的影响。方法：采用多种动物分别建立了不同致伤方式诱发脓毒症及多脏器功能失常综合征（MODS）的模型；并结合临床病例进行前瞻性研究。结果：分别应用杀菌-通透性增加蛋白、抗核心脂多糖（LPS）单抗及Re型LPS抗血清、低剂量多粘菌素B、选择性消化道脱污染及抗肿瘤坏死因子（TNF）单抗等措施，可显著中和循环内毒素，能有效地减轻肝、肺、肾及肠道等器官损害和明显提高动物存活率；并且抗内毒素可不同程度地抑制循环和组织中细胞因子mRNA及蛋白质的表达和改善机体细胞免疫功能；临床观察显示，大面积烧伤和创伤患者24小时内血浆内毒素含量显著升高，其升高程度与血浆TNF呈正相关，这一趋势以并发脓毒症、MODS者尤为明显。结论：肠源性内毒素血症与脓毒症、脏器功能损害密切相关；创伤早期采取有效措施及时防止肠源性内毒素血症对创伤所致脓毒症及MODS具有一定的防护效应，动物预后明显改善；其作用机制与抑制细胞因子的基因表达、分泌及提高机体全身免疫状况有关。

Study on the significance of intervention strategies against endotoxemia following hemorrhage,trauma and burns

Objective:To investigate the influence of gut - derived endotoxemia on proinflammatorycytokine formation,systemic immunosuppression,and multiple organ dysfunction after trauma by use ofvarious anti - endotoxin strategies. Methods: Sepsis and multiple organ dysfunction syndrome (MODS)models associated with hemorrhagic shock, thermal injury,intestinal ischemia - reperfusion as well ascombined injury were used in these serial studies. Also,our prospective studies included patients withextensive burns,polytrauma,major surgery,and healthy volunteers who served as a comparison group.Results: It was shown that both portal and systemic endotoxin levels were significantly reduced at different time points after acute insults in animals that treated by measures aiming at controlling endotoxemia, including recombinant bactericidal - permeability increasing protein, anti - core lipopolysaccharide(LPS) monoclonal antibody,Re - LPS antiserum,low - dose of polymyxin B,selective decontaminationof the digestive tract, and monoclonal antibody to tumor necrosis factor (TNF). Meanwhile, treatmentwith novel anti -endotoxin measures could markedly attenuate multiple organ damage,improve systemiccell - mediated immunity and the survival rate,and inhibit proinflammatory cytokine gene expression aswell as protein induction. On the other hand,plasma endotoxin levels in patients with extensive burns,polytrauma,and major surgery significantly elevated within 24 hours following injuries,and they wereclosely correlated with plasma TNF values,particularly in those who developed sepsis and MODS. Conclusions:These data suggest that a relationship indeed exists between endotoxemia and traumatic sepsisand MODS. Early use of anti -- endotoxin measures is effective in preventing the development of sepsisand remote organ dysfunction secondary to various insults,which may be associated with inhibition ofproinflammatory cytokine gene expression as well as protein induction, and improvement of immunefunction.