脓毒症治疗------机遇与挑战并存 - 第三军医大学学报.doc

脓毒症治疗——机遇与挑战并存 周 红1，刘 鑫2，郑 江2 （400038 重庆，第三军医大学：医学检验系暨药学院药理学教研室1，西南医院综合实验研究中心2） [关键词] 脓毒症；治疗；新药研究 [中图法分类号] [文献标志码] A Sepsis TreatmentChance and Challenge Zhou Hong 1，Liu Xin 2，Zheng Jiang2(1 Medical Research Center, Southwest Hospital, the Third Military Medical University, Chongqing 400038, P. R. China; 2 Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing 400038, P. R. China) [Abstract] Sepsis related organ dysfunction and shock are primary causes of death in critical illness, which is triggered by Pathogen Associated Molecules Patterns (PAMPs) and progress into life threatening stages as a result of systemic dysfunction in inflammatory reactions, coagulation cascades and immune response. Advances in our understanding of the pathogenesis in sepsis prompt different kinds of anti-sepsis strategies. Unfortunately, there is no specific agent for sepsis except the withdrawal human recombinant activated protein C. Therefore, it is significant to reevaluate the drugs in clinic and rethink the strategies in preclinical or clinical studies. Herein, we discuss the therapeutic approach to sepsis that affects different stages of sepsis progression and their efficacy in treating sepsis, and the possible fields to get new agents to treat sepsis. [Key words] sepsis; drugs; Pathogen Associated Molecules Patterns 脓毒症（sepsis）是由感染因素导致的全身炎症反应综合征，是严重创（烧、战）伤、休克、感染、内/外科重症患者常见的并发症，进一步发展可导致脓毒症休克（septic shock）、多器官功能障碍综合征（MODS），是临床危重患者的最主要死亡原因之一。虽然现代救治技术有了长足进展，但脓毒症患者的死亡率并未进一步降低，因此脓毒症治疗已成为现代危重病医学面临的突出难题，为此全球脓毒症联盟将2012年9月13日首个世界脓毒症日recombinant activated protein C，hrAPC）也因疗效不确切于2011年10月撤市[2-3]。因此，人们对脓毒症的防治措施的研究信心受到极大打击，重新审视现有的临床治疗措施和新药研究状况对深入研究脓毒症发病的病理生理学机制和重拾脓毒症治疗的信心具有重要意义。 1 脓毒症发病的病理生理学 脓毒症的发生与感染因素或者严重组织损伤诱导的先天免疫系统活化、从而导致炎症介质过度释放有关，补体系统活化和细胞免疫的过度活化是脓毒症的特征。中性粒细胞和巨噬细胞对细胞因子、趋化因子、补体活化产物以及其他介质的反应，产生更多的次级炎症介质如氧自由基，进一步放大