Therapy Of Septic Animal Through Inhibtion Of Innate Immunity

Sepsis shock is kind of acute and systemic inflammatory response,which can lead to multiple organ damage and failure,septic shock or even death.At present the clinical treatment to sepsis is not efficient and mortality of sepsis patients is still very high.In acute inflammation period of sepsis,the innate immunity is strongly activated and produces abundant inflammatory cytokines produced,which results severe organ damage.Therefore,study of the pathogenesis of sepsis and investigation of the methods to reduce the mortality are most important in sepsis research.The aim of this study is to use lymph drainage and inhibit macrophage pyroptosis through autophgy activation to control inflammation,protect tissue from immune injury and rescue the septic animals.In this study,we established the CLP(Cecal Ligation and Puncture)sepsis model and identified different anesthetics using chloral hydrate and isoflurane effected the mortality of sepsis rats.Additionally,thoracic duct lymph drainage model was successfully established on the basis of CLP model.Based these two animal models,we detected the concentration of proinflammatory factors in lymph,the toxic effects on pulmonary macrophage to find the right time for lymph drainage.By detecting the changes of the concentration of proinflammatory factors in biood of sepsic rats with lymph drainage and their histopathology,we evaluated the effects of lymph drainage on reduction of inflammation and treatment of sepsis.Results show that the concentration of inflammatory cytokines in lymph increased significantly 6 hours post CLP surgery,and induced remarkable cytotoxicity on pulmonary macrophage.Lymph drainage decreased the concentration of inflammatory cytokines in blood,protected the tissue damage and reduced the mortality of sepsis animals.The present study illustrated that lymph drainage is an effective method for treatment of sepsis.It is well accepted that inhibition of inflammsome activation and pyroptosis is helpful to rescue septic animals.We used rapamycin to inhibit the pyroptosis of peritoneal macrophages caused by intestinal content infection.Results confirmed that activation of autophgy by rapamycin effectively inhibited pyroptosis and the secretion of inflammatory cytokine in vitro.Moreover,intraperitoneal injection of rapamycin 24 hours before the CLP surgery can effectively increase the survival rate of sepsis animal.