Protective Effect And Mechanism Of Compound Glutamine Entersoluble Capsules On 5-FU Induced Intestinal Mucositis In Mice

Objective: The purpose of this study is to establish an animal model of intestinal mucositis induced by 5-fluorouracil(5-FU)in mice,and then to explore the protective effect and mechanism of Compound Glutamin Entersoluble Capsules(CGEC)on chemotherapy-induced intestinal mucositis and to provide basis for clinical application.Methods:(1)Establishment of intestinal mucositis model induced by 5-fluorouracil in mice: The different doses of 5-FU were intraperitoneally injected into mice by 1day or 5 consecutive days.The body weight,diarrhea score and food intake of mice were recorded daily,and the pathological changes of small intestinal tissue were detected after the last administration of 1 day or 3 days.(2)Protective effect of CGEC on 5-FU induced intestinal mucositis in mice: Intestinal mucositis induced by 5-FU(50 mg/kg)in mice by intraperitoneal injection for 5 days.ICR male mices were randomized into7 groups: normal group,model group,montmorillonite powder group(1.5g/kg),Gln group(1.92 g/kg),the three groups of CGEC(3.2,1.6,0.8 g/kg),administrated by oral gavage for 13 days.The body weight,diarrhea score and food intake of mice were recorded daily,the pathological changes of small intestinal tissue were observe by hematoxylin eosin(HE)staining,and the villous height and crypt depth were measured.(3)Study on the mechanism of CGEC on 5-FU induced intestinal mucositis in mice: Bacterial translocation of spleen was observed by bacterial culture.Serum content of endotoxin(ET),Diamine oxidase(DAO),D-lactate and the level of sIgA in small intestinal tissue were detected by ELISA.The expression of occludin,claudin-1,ZO-1 protein of small intestinal tissue were detected by immunohistochemical method.Results:(1)Establishment of intestinal mucositis model induced by 5-fluorouracil in mice: Compared to the control group,each dosage group showed various degrees of body weight loss,diarrhea and reduce of food intake after administered 5-FU.And the results demonstrated evident pathological characteristics in small intestine at the single dose of 400 mg/kg and the consecutive injection of 50 mg/kg,100 mg/kg,butthe mortality rate was 100% due to the high dose in the 100 mg/kg group.(2)Protective effect of CGEC on 5-FU induced intestinal mucositis in mice: Compared to the model group,the dose groups of CGEC(3.2,1.6 g/kg)could significantly increase the body weight and reduce the score of diarrhea(P<0.05 or P<0.01),increase intestinal villus height and crypt depth(P<0.01),and improve intestinal mucosal pathological damage.(3)The mechanism of CGEC on 5-FU induced intestinal mucositis in mice: Compared to the model group,the dose groups of CGEC(3.2,1.6g/kg)could significantly decrease the rate of bacterial translocation and the content of serum DAO,ET,D-lactic acid(P<0.05 or P<0.01),and improve intestinal permeability status of mice.The dose group of CGEC(3.2 g/kg)could significantly increase the content of sIgA in small intestinal tissue of mice(P<0.05).And CGEC could increase the expression of occludin,claudin-1 and ZO-1 tight junction protein in small intestinal tissue of mice.Conclusion: CGEC colud improve intestinal mucositis induced by 5-FU,reduce the bacterial translocation rate and the level of serum ET,DAO and D-lactate in mice to improve intestinal permeability,and increase the expression of occludin,claudin-1and ZO-1 tight junction protein to protect the intestinal mucosal barrier injury.CGEC could increase the level of sIgA in small intestinal tissue to enhance intestinal immunity.