Study On Function And Mechanism Of NLRP3 Inflammasome Signaling Pathway In Acute Lung Injury Induced By Seawater

Background:In our daily life,seawater drowning has always been a serious hidden danger to social security,which will cause a large number of losses both in life and money every year.Compared with freshwater drowning,the seawater drowning-induced lung injury is more serious and difficult to treat.Moreover,patients are prone to seawater drowning-induced acute lung injury(SW-ALI)after inhalation.In severe cases,it may develop into seawater drowning-induced acute respiratory distress syndrome(SW-ARDS)with severe state of illness and high mortality due to the high permeability,high electrolyte,low temperature and alkalinity of seawater,which will significantly cause more damage to human body.However,the research results on seawater drowning-induced lung injury lack theoretical basis and relevant basic theories,and the similarities and differences between the pathogenesis and other factors leading to lung injury are not very clear.Therefore,the relevant theoretical system has not been formed yet,so some opinions are put forward through this experimental study,in the hope of providing some theoretical basis for the clinical treatment of seawater drowning-induced lung injury.NLRP3 inflammasome is a multi-protein complex assembled by cytoplasmic pattern recognition receptor(PRR),which can recognize pathogen-associated molecular patterns(PAMPs)or danger-associated molecular patterns(DAMPs),recruit and activate proinflammatory protease caspase-1 and activated caspase-1,cut the precursors of IL-1β and IL-18,produce a large number of relatively mature inflammatory mediators,cause severe inflammation in the body and promote the occurrence and development of various inflammatory diseases.Therefore,we speculate that NLRP3 inflammasome may play an important role in the pathogenesis of seawater drowning-induced lung injury.In this study,we observe the effect of NLRP3 inflammasome signal channel and the change of its downstream inflammatory factors on lung injury after seawater inhalation through rat seawater drowning-induced acute lung injury model,trying to expound the role and mechanism of NLRP3 inflammasome in the inflammatory reaction of seawater drowning-induced acute lung injury and putting forward some new ideas for the diagnosis and treatment of seawater drowning-induced acute lung injury.Research significance:Based on the fact that the composition of seawater is complex and the damage of seawater to human body is more serious than that of freshwater,and the relevant research results lack theoretical basis and relevant basic theories,this project proposes and validates that NLRP3 inflammosome signal channel may play an important role in the pathogenesis of seawater drowning-induced lung injury,which provides a new idea for further improving the pathogenesis and theory of seawater drowning-induced lung injury and openning up a new clinical treatment program.Methods:1.A seawater drowning-induced lung injury model is established,and the degree of lung injury at different time is observed and evaluated,providing the basis for selecting the appropriate time for subsequent experiments.2.After the successful establishment of rat seawater drowning-induced acute lung injury model,the expression levels of NLRP3,Caspase-1 and other inflammasome signals in lung tissues,as well as the expression levels of inflammatory factors such as IL-1β and IL-18 in alveolar lavage fluid and lung tissues are detected,and the activation of NLRP3 inflammasome after seawater inhalation is discussed,providing a basis for determining the appropriate time for subsequent relevant inhibition experiments.3.NLRP3 inflammasome inhibitor is administered by intratracheal instillation,and the effect of NLRP3 inflammasome inhibitor on the activation of NLRP3 inflammasome signal channel of rats with acute lung injury.By observing lung pathological section and indicators of lung injury,the effect of NLRP3 inflammasome inhibitor on rats with seawater drowning-induced acute lung injury is studied and the role of NLRP3 inflammasome in seawater drowning-induced lung injury.4.Through the use of histone inhibitor,the activation of NLRP3 inflammasome signal channel in lung tissues after seawater inhalation is observed,and the role of histone in the activation of NLRP3 inflammasome after seawater inhalation is clarified.Results:1.After seawater drowning-induced acute lung injury,inflammasome signals such as NLRP3 and Caspase-1,as well as the expression levels of IL-1β,IL-18 and other inflammatory factors in lung tissues show time independence after seawater inhalation,rising gradually and reaching the peak around 6h,then falling gradually.By the way,the level of histone increases gradually.2.After intratracheal instillation of NLRP3 inflammasome inhibitor GB-11300,inflammasome signals such as NLRP3 and Caspase-1,as well as the expression levels of IL-1β,IL-18 and other inflammatory factors in lung tissues of rats after seawater inhalation are significantly inhibited.Moreover,the inhibition of the activation of NLRP3 inflammasome can significantly alleviate the lung pathological damage caused by seawater inhalation and reduce the level of lung inflammation.3.After the use of histone inhibitors,the activation of NLRP3 inflammasome in lung tissues of rats by seawater is significantly inhibited,suggesting that the activation of NLRP3 inflammasome after seawater inhalation may be histone dependent.Conclusions:After seawater drowning-induced acute lung injury,NLRP3 inflammasome signal channel in lung tissues can be activated,and the activated NLRP3 inflammasome can further promote the expressions of IL-1β,IL-18 and other inflammatory factors,thereby enlarging the inflammatory reaction and leading to lung injury.Moreover,the activation of NLRP3 inflammasome in seawater drowning-induced lung injury is a process of histone dependence,and the inhibition of the activation of NLRP3 inflammasome or the removal of extracellular histone can effectively alleviate lung injury.