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线粒体自噬影响巨噬细胞极化在脓毒症免疫调节中的作用及中医药干预研究进展

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Role of mitochondrial autophagy affecting macrophage polarization in sepsis immunomodulation and Traditional Chinese Medicine Prevention and Treatment:A Review

摘要: 脓毒症是一种由感染引起的器官功能障碍综合征,具有发病率高、致死率高的特点,发病机制复杂,可触发连锁的免疫反应,且暂无特效药物。目前,脓毒症的治疗多采用抗生素、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小时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不受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。值得注意的是,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。中药单体、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PINK1、Parkin、LC3、P62等的水平,动态平衡巨噬细胞M1与M2的比例,达到预防、扭转甚至截断脓毒症病情进展的效果,为脓毒症提供了一个未病先防、既病防变的新思路。
Abstract: Sepsis is an infection-induced organ dysfunction syndrome characterized by high morbidity and mortality, with a complex pathogenesis that triggers a chain of immune responses, and for the time being, there is no specific drug. Currently, sepsis is mostly treated with antibiotics, hemodynamic management, mechanical ventilation, and other Western supportive therapy, but with the emergence of the immune chain reaction, the patient's susceptibility to secondary infections increases significantly, and it is highly likely to develop into septic shock with a poor prognosis. The international consensus suggests that initiating dynamic monitoring of the patient's immune function within 48 hours after the diagnosis of sepsis can effectively slow down the sepsis process. Numerous studies have pointed out that macrophages, as the first line of defense of the innate immune system against pathogens, can play an important role in the treatment of various immune system diseases by regulating the ratio of polarization to cytokine activation. Mitochondrial autophagy, as a research hotspot in recent years, has been increasingly evidenced to play a key role in the regulation of inflammatory signaling. On the one hand, promoting mitochondrial autophagy in the inflammatory storm phase can attenuate uncontrolled infection and excessive inflammation in sepsis; on the other hand, inhibiting mitochondrial autophagy in the immunosuppressive phase can enhance the body's immunity, promote the clearance of bacteria and improve the survival rate of patients. It is worth noting that Traditional Chinese medicine, has inherited the idea of "treating the future disease", which coincides with the concept of "prevention and interruption" in the current expert consensus on sepsis. Traditional Chinese medicine treatments, such as Chinese medicine monomers, compound prescriptions, and acupuncture, start from the treatment of clearing heat and removing toxins, activating blood circulation and removing blood stasis, supporting the root of the disease, and promoting the internal and external attack, and bi-directionally regulate the levels of mitochondrial autophagy-related proteins such as PINK1, Parkin, LC3, P62, etc., and dynamically balance the ratio of macrophage M1 to M2, to achieve the effect of preventing, reversing, and even interrupting the progression of the disease, and to provide an alternative to the current expert consensus on the prevention and blockage of sepsis, a new idea of preventing sepsis before it occurs and preventing it from occurring in the first place.

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[V1] 2023-11-23 14:03:32 ChinaXiv:202311.00257V1 下载全文
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