Experimental Study On Therapy Of Sepsis Through Autophagy Inhibiting Pyroptosis

Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host response to infection.The excessive activation of inflammasomes caused pyroptosis in some immune cells,which aggravate the inflammatory response.The aim of this study is to reduce the excessive activation of pyroptosis caused by bacteria entering the lung by inducing autophagy,in order to reduce tissue inflammatory injury as well as the mortality of sepsis.Study confirmed that there exists gut microbial translocation in pulmonary in the early stage of sepsis,which leads to the activation of inflammasomes and pyroptosis.However,it is still unknown how gut microbiota translocate into the lung.This study explored the role of lymph circulation in sepsis induced gut microbiota translocate into the lung through high-throughput sequencing technology.The results showed that the number and species of microflora in lymph increased gradually with time,and reached its peak at 8h,lymphatic drainage significantly alleviated the inflammatory damage of the lung tissue.It indicates that lymphatic circulation plays an important role in the translocation of intestinal microbes into the lung.In order to determine the effect of intestinal microbiota entering the lung on inflammatory response in lung macrophages,and explore the feasibility of relieving sepsis induced acute lung injury by the activation of autophagy and inhibiting pyroptosis.We first used rapamycin to induceautophagy in macrophages in vitro.The effects of autophagy on pyroptosis were evaluated by detecting the activation of inflammasomes and the mortality of macrophages after stimulated by cecal contents.In order to further study the effects of autophagy in septic animals,the CLP model was established in mice.We evaluated the therapeutic effects of autophagy on the sepsis by detecting the activation of inflammasomes,morphological changes of the tissues.The results showed that after the activation of autophagy,the activation of inflammasomes,the release of inflammatory cytokines and the pyroptosis in macrophages were significantly decreased;the activation of inflammasomes and the inflammatory injury was evidently alleviated in the tissues of septic mice,the survival rate of mice was also improved markedly.It proved that the inhibitory effect of autophagy in pyroptosis is a effective way in sepsis treatment.