The Significance Of S100A8/A9in Neonatal Rats Sepsis

Objective: Neonates are susceptible to bacterial infection, which lead to highmorbidity and mortality from sepsis.The innate immune system represents the first line ofdefense against invading pathogens and other external harmful agents.The patternrecognition receptors(PRRs) of innate immune cells not just can recognizepathogen-associated molecular patterns(PAMPs),but recognize Damage-associatedmolecular patterns(DAMPs).Then, immune system initiates responses.S100A8/A9,aheterodimeric complex has been identified as important DAMPs released by activatedphagocytes. S100A8/A9plays important roles in inflammation.In this study, we establishthe model of neonatal rats’ sepsis to analyse the variation of S100A8/A9heterodimer andcytokine TNF-ɑ、IL-6.The all is in order to investigate the role of S100A8/A9in thepathogenesis of sepsis of neonatal rats,and try to develop a new idea of immunomodulationand intervention in neonatal sepsis.Methods: Choosing randomly367-day-old Sprague-Dawley(SD) rats with SpecialPathogen Free(SPF), the animals received an intraperitoneal injection of LPS to establishthe sepsis group.Other36rats received an intraperitoneal injection of the same amount ofNS to establish the control group.Then，the two groups rats were randomly assigned todifferent time points,including2,4,8,12,24,48hours.And there were6neonatal rats in eachtime point.At each target time point,we got the the lungs and livers for analysis. Real-timePCR was chosen to analyze the mRNA expression of S100A8、S100A9、TNF-ɑandIL-6.Immunohistochemistry was chosen to analyze the expression of S100A8/A9in thelungs and livers.Results:1. The results of Real-time PCR indicate the variation trend of theS100A8mRNA、S100A9mRNA、TNF-ɑ mRNA in the lungs and livers of sepsis group wasbasically similar. Compared to the control group,in the lungs and livers of the sepsisgroup,S100A8mRNA presented higher level at the second hour(P<0.01),and reached apeak about8hours, to48hours has been at a high level;S100A9mRNA presented higher level at the second hour(P<0.01),and reached a peak about12hours, to48hours of theexperiment kept at higher level.TNF-ɑ mRNApresented higher level at the secondhour(P<0.01),and reached a peak about12hours, to48hours kept at a high level;2. In thelungs of sepsis group,IL-6mRNA presented higher level at the fourth hour,reached a peakabout8hours, to48hours has been at a high level;In the livers of sepsis group,IL-6mRNApresented higher level at the fourth hour(P<0.01),and stepped up gradually to12hours,andkept at a high level to48hours.3.The results of immunohistochemistry indicate thatS100A8/A9heterodimer expression in the lungs and livers of the sepsis group presentedhigher level at the second hour(P<0.01),then stepped up gradually to24hours,and kept athigher level to48hours.Conclusion:1.With the progress of the experiment,the damage of lungs and livers ofneonatal sepsis rats got more and more serious,and the expression level of cytokineTNF-ɑ、IL-6increased,which indicated inflammatory damage was the main feature ofneonatal sepsis in early phase.2.The expression level of S100A8/A9heterodimer in theinflammatory rats increased with time-dependent in the progress of sepsis,indicatedS100A8/A9involve in inflammatory response of neonatal sepsis.3. There was a positivecorrelation between the expression level of S100A8/A9heterodimer and cytokine TNF-ɑ、IL-6in the inflammatory rats,which indicated the synergies between S100A8/A9andcytokine in organ damage of neonatal sepsis.