[Role of Mitophagy Affecting Macrophage Polarization in Immunomodulationin Sepsis and Traditional Chinese Medicine Intervention:A Review].

Abstract

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.