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