Sepsis induces albuminuria and alterations in the glomerular filtration barrier a morphofunctional study in the rat 英文参考文献.docVIP

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Sepsis induces albuminuria and alterations in the glomerular filtration barrier a morphofunctional study in the rat 英文参考文献.doc

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Sepsis induces albuminuria and alterations in the glomerular filtration barrier a morphofunctional study in the rat 英文参考文献

Adembrietal.CriticalCare2011,15:R277 /content/15/6/R277 RESEARCH OpenAccess Sepsisinducesalbuminuriaandalterationsinthe glomerularfiltrationbarrier:amorphofunctional studyintherat ChiaraAdembri1*,EleonoraSgambati2,LucaVitali1,ValentinaSelmi1,MartinaMargheri3,AlessiaTani3, LauraBonaccini3,DanieleNosi3,AnnaLCaldini4,LuciaFormigli3andAngeloRDeGaudio1 Abstract Introduction:Increasedvascularpermeabilityrepresentsoneofthehallmarksofsepsis.Inthekidney,vascular permeabilityisstrictlyregulatedbythe‘glomerularfiltrationbarrier’(GFB),whichiscomprisedofglomerular endothelium,podocytes,theirinterposedbasementmembranesandtheassociatedglycocalyx.Althoughitislikely thattheGFBanditsglycocalyxarealteredduringsepsis,nostudyhasspecificallyaddressedthisissue.Theaimof thisstudywastoevaluatewhetheralbuminuria–thehallmarkofGFBperm-selectivity–occursintheinitialstage ofsepsisandwhetheritisassociatedwithmorphologicalandbiochemicalchangesoftheGFB. Methods:Cecalligationandpuncture(CLP)wasusedtoinducesepsisintherat.Tumornecrosisfactor(TNF)- alphalevelsinplasmaandgrowthofmicroorganismsintheperitonealfluidwereevaluatedat0,3and7hours afterCLPorsham-operation.Atthesametimes,kidneyspecimenswerecollectedandstructuralandultrastructural alterationsintheGFBwereassessed.Inaddition,severalcomponentsofGFB-associatedglycocalyx,syndecan-1, hyluronan(HA)andsialicacidswereevaluatedbyimmunofluorescence,immunohistochemistryandlectin histochemistrytechniques.Serumcreatinineandcreatinineclearanceweremeasuredtoassesskidneyfunctionand albuminuriaforchangesinGFBpermeability.AnalysisofvariancefollowedbyTukey’smultiplecomparisontestwas used. Results:SepticratsshowedincreasedTNF-alphalevelsandgrowthofmicroorganismsintheperitonealfluid.Only afewrenalcorpuscleshadmajorultrastructuralandstructuralalterationsandnochangeinserumcreatinineor creatinineclearancewasobserved.Contrarily,urinaryalbuminsignificantlyincreasedafterCLPandwasassociated withdiffusealterationintheglycocalyxoftheGFB,whichconsistedinadecreaseinsyndecan-1exp