Effects Of Citrulline On Intestinal Barrier Dysfunction Of Aged Rats In Sepsis

ObjectiveSepsis is the most important reason of elderly patients in the intensive care unit,and intestinal barrier dysfunction becomes a key link in the development of elderly sepsis.At present,the mechanism of intestinal barrier dysfunction induced by sepsis have not been clarified exactly,and the effectiveness of interventions have not been verified yet.The data of old animal model is also extremely scarce.This study designed to survey the changes of the intestinal barrier function in elderly rats with sepsis and the effects of different immunonutritional interventions with aim to provide experimental guidance for the effective treatment of intestinal barrier dysfunction.MethodsIn our study,80 elderly SD rats were divided into 6 groups:Control group(Control),Sham group(Sham),cecal ligation and puncture(CLP),CLP+arginine(ARG),CLP+glutamine(GLN),CLP+citrulline(CIT).The CIT,ARG,GLN group received a diet containing 0.6%citrulline(lg/kg),arginine(0.992g/kg),glutamine(0.8g/kg)respectively;the CLP,Sham,Control groups were fed a standard chow diet.On the eighth day of treatment,caecum was ligated and punctured except the Sham group,which only underwent laparotomy.After 4,8,and 24 hours,blood was collected to measure I-FABP,DAO,D-lactate and cytokines.Intestinal fluid were collected to measure sIgA.Samples of caecum were removed 4,8,and 24 hours after CLP for histological analysis.The survival rate of Sham and CLP groups were also compared.Results1.Effects of citrulline on intestinal mechanical barrier function of CLP aged rats.1.1 Small intestinal villus height and surface area of CIT group were significantly higher than that of CLP group and ARG group(P<0.01).These results were also proved by histological analysis.1.2 In CIT group,Serum I-FABP,DAO and D-Lac values were significantly lower than that of CLP group and ARG group(P<0.05).2.Effects of citrulline intestinal immune barrier function of CLP aged rats.2.1 Serum IFN-y:IL-10 ratio of CIT and ARG groups were lower than that of Control and Sham group(P<0.05).2.2 The values of intestinal fluid sIgA of CIT,ARG and GLN group were similar and significantly higher than that of CLP and sham group(P<0.01).3.Evaluation of intestinal function in aged rats with serum citrulline levels3.1 Intestinal function of aged rats was impaired after CLP.In CLP group,Serum citrulline values were significantly lower than that of Control group and Sham group(P<0.01).3.2 The correlation between serum citrulline values and intestinal mechanical barrier function:I-FABP(r=-0.672,P=0.000),DAO(r=-0.788,P=0.000),D-Lac(r=-0.717,P=0.000).There might exsit negative correlation between serum citrulline values and intestinal mechanical barrier function index.The correlation between serum citrulline values and villus height(r=0.710,P=0.000),small intestinal villus surface area(r=0.709,p=0.000).There might exsit positive correlation between serum citrulline values and intestine constructure.3.3 The correlation between serum citrulline values and intestinal immune barrier function:IFN-γ:IL-10 ratio(r=-0.428,p=0.023),sIgA(r=0.660,p=0.000).There might exsit negative correlation between serum citrulline values and serum IFN-y:IL-10 ratio andthere might exsit positive correlation between serum citrulline values and intestinal fluid sIgA levels.Conclusion1.Pretreatment with citrulline improves gut mechanical barrier after CLP in rat.Citrulline is better than arginine.2.Pretreatment with citrulline improves gut immune barrier after CLP in rat.3.Serum citrulline levels is a suitable biomarker of intestinal function in aged rats.