【摘要】 脓毒症是临床常见的急危重症之一,有病情进展迅速、病死率高等特点,其发病机制复杂,至今仍是重症医学研究中的重点和难点。弥散性血管内凝血(DIC)是脓毒症最常见的严重并发症之一,常表现为凝血系统的广泛激活和微血栓形成,显著提高病死率。凝血因子Ⅻ(FⅫ)是一种丝氨酸蛋白酶,被认为有减少血栓形成而不增加出血风险的潜力。研究表明,中性粒细胞胞外诱捕网(NET)是一种由中性粒细胞通过NET形成过程释放的DNA网络结构,能提供带负电荷的支架,促进FⅫ的结合与激活,从而触发内源性凝血级联反应,在脓毒症中参与高凝状态的形成。近年来,越来越多的研究聚焦于NET与FⅫ在脓毒症并发DIC过程中的交互机制,揭示其在血管内血栓形成与凝血系统激活中的关键作用。NET不仅作为物理屏障捕获病原体,还可通过释放髓过氧化物酶(MPO)、中性粒细胞弹性酶(NE)和活性氧(ROS)等促炎因子,加剧组织损伤与凝血激活。FⅫ的激活可进一步启动激肽释放酶-激肽系统(KKS)及FⅪ,增强炎症反应与血栓形成,形成恶性循环。中医药作为我国传统医学的重要组成部分,在脓毒症及其并发症的治疗中展现出独特优势。基于“扶正祛邪”“益气活血”等理论,通过调节机体免疫状态和改善凝血功能紊乱,有望干预由NET和FⅫ介导的高凝状态,从而延缓DIC进展,改善患者预后。目前已有研究证实,多种中药如丹参、黄芪、大黄、川芎、姜黄等有抗凝、抑制血小板聚集和抗炎作用;此外,血必净注射液、清瘟败毒饮等中药复方在调节凝血因子水平、降低D-二聚体浓度及改善器官功能方面亦显示出良好疗效。目前针对中医药干预NET形成及FⅫ激活的研究尚不充分,其潜在机制与临床应用价值仍值得深入探索。本文总结了FⅫ和NET在脓毒症并发DIC中的关键作用及其相互关系,并探讨中医药在该领域的研究进展,旨在为脓毒症并发DIC作用的机制研究及中西医结合干预提供新的思路和方向。更多还原

【Abstract】 Sepsis is a common critical illness in clinical practice, characterized by rapid progression and high mortality. Its complex pathogenesis remains a major focus and challenge in the field of critical care medicine. Disseminated intravascular coagulation(DIC) is one of the most frequent and severe complications of sepsis, featuring systemic activation of the coagulation cascade and microthrombus formation, significantly increasing the mortality. Coagulation factor Ⅻ(FⅫ), a serine protease, is considered to have therapeutic potential for thrombosis without impairing normal hemostasis. Study reveal that neutrophil extracellular trap(NET), web-like DNA structures released through a unique process known as NETosis, provide negatively charged scaffolds that promote FⅫ binding and activation, thus triggering the intrinsic coagulation cascade and contributing to a hypercoagulable state. In recent years, increasing attention has been paid to the interaction between NET and FⅫ in sepsis complicated with DIC. These 2 factors play central roles in intravascular thrombus formation and coagulation activation. Beyond their antimicrobial function, NET can aggravate tissue injury and coagulation abnormalities by releasing proinflammatory mediators such as myeloperoxidase(MPO), neutrophil elastase(NE), and reactive oxygen species(ROS). FⅫ activation can further trigger the kallikrein-kinin system(KKS) and activate FⅪ, amplifying inflammation and thrombosis in a vicious cycle. Traditional Chinese medicine(TCM), as a key component of Chinese medical heritage, has demonstrated unique advantages in managing sepsis and its complications. Based on therapeutic principles such as "strengthening healthy qi and eliminating pathogenic factors" and "tonifying qi and activating blood circulation", TCM is believed to regulate immune function and correct coagulation disorders, thereby interfering with the hypercoagulable state mediated by NET and FⅫ, slowing the progression of DIC, and improving clinical outcomes. Several herbs, including Salvia miltiorrhiza, Astragalus membranaceus, Rheum officinale, Ligusticum chuanxiong, and Curcuma longa, have shown anticoagulant, antiplatelet, and anti-inflammatory properties. In addition, compound formulations such as Xuebijing injection and Qingwen Baidu decoction have demonstrated clinical efficacy in improving coagulation parameters, reducing D-dimer levels, and protecting organ function. Although current evidence on the effects of TCM on NET formation and FⅫ activation is still limited, its potential mechanisms and clinical value warrant further investigation. This review summarizes the critical roles and interplay of FⅫ and NET in sepsis complicated with DIC and discusses the advances in TCM-based interventions, aiming to provide new perspectives for mechanism-oriented research and integrative therapeutic strategies.更多还原