Sepsis,a syndrome characterized by organ dysfunction caused by infection,exhibits high incidence and mortality.The pathogenesis of sepsis is complex and involves a cascade of immune reactions,with no specific drugs currently available.Sepsis is mainly treated with Western medical supportive therapies such as antibiotics,hemodynamic management,and mechanical ventilation.However,the occurrence of immune cascades significantly increases patients' vulnerability to secondary infections,leading to septic shock and unfavorable prognoses.International consensus indicates that initiating dynamic monitoring of patients' immune function within 48 h post-sepsis diagnosis can effectively decelerate sepsis progression.Extensive studies have indicated that macrophages,serving as the first line of defense in the innate immune system against pathogens,play a vital role in treating immune system disorders by regulating macrophage polarization and the ratio of cytokines activated.Mitophagy,a hot topic in recent years,has increasingly been shown to play a crucial role in regulating inflammatory signal transduction.Promoting mitophagy during the stage of cytokine storm can mitigate uncontrolled infection and excessive inflammation in sepsis,and inhibiting mitophagy during immunosuppression can enhance host immunity,facilitate bacterial clearance,and improve the survival rate of patients.The idea of treating disease before its onset in traditional Chinese medicine (TCM) coincides with the current consensus among sepsis experts on prevention and interception.The TCM therapies such as extracts of Chinese medicine decoction pieces,TCM compound prescriptions,and acupuncture and moxibustion have the effects of clearing heat and detoxifying,activating blood and resolving stasis,reinforcing healthy qi and consolidating root,and purging.These approaches dynamically regulate the levels of mitophagy-related proteins,such as phosphatase and tension homology-induced putative kinase 1,Parkin-E3 ubiquitin protein ligase,light chain 3,and p62,while maintaining a suitable ratio between M1 and M2 macrophages.Consequently,they effectively prevent,halt,or even reverse the progression of sepsis,offering a novel perspective on sepsis management by emphasizing prevention before disease onset and controlling development of existing disease.
脓毒症是一种由感染引起的器官功能障碍综合征,具有高发病率、高致死率的特点,发病机制复杂,可触发连锁的免疫反应,且暂无特效药物。其治疗多采用抗生素、血流动力学管理、机械通气等西医支持治疗,但随着免疫连锁反应的出现,患者对继发感染的易感性显著增加,极易发展为脓毒症休克,预后较差。国际共识提出,在脓毒症确诊后的48 h内启动对患者免疫功能的动态监测可有效减缓脓毒症进程。大量研究指出,巨噬细胞作为先天免疫系统抵御病原体的第一道防线,可通过调控巨噬细胞极化与细胞因子的激活比例,在多种免疫系统疾病的治疗中发挥重要作用。而线粒体自噬作为近年来的研究热点,越来越多的证据表明,其在炎症信号传导的调节中起着关键作用。一方面,在炎症风暴期,促进线粒体自噬可减轻脓毒症难以控制的感染和过度炎症;另一方面,在免疫抑制期,抑制线粒体自噬可提高机体免疫力,促进清除细菌并提高患者存活率。中医作为祖国传统医学,其“治未病”的思想传承与现行脓毒症专家共识中“预防与阻断”的理念不谋而合。中药饮片提取物、中药复方及针灸等中医药治疗手段,从清热解毒、活血化瘀、扶正固本、通里攻下的治法入手,双向调节线粒体自噬相关蛋白磷酸酶及张力蛋白同源基因诱导激酶1、帕金森-E3泛素连接酶、轻链3、p62等的水平,动态调节巨噬细胞M1与M2的比例,达到预防、阻断甚至逆转脓毒症病情进展的效果,为脓毒症治疗提供一个未病先防、既病防变的新思路。.
Keywords: immunomodulation; mitophagy; polarization of macrophages; sepsis; traditional Chinese medicine.