Effects Of Dietary Restriction On Intestinal Barrier,Infection And Survival Rate After Chemotherapy In Mice

Background:With the increase of population size and the aging of the population,the incidence of malignant tumors has increased significantly,which has become one of the main causes of disease death among Chinese residents.At present,chemotherapy is still an important cornerstone of the treatment of malignant tumors.Older patients who receive standard-dose-intensity chemotherapy tend to be more likely to cause serious infections and even be life-threatening than younger patients.As a result,the relative dose intensity of chemotherapy in elderly patients with malignant tumors is often lower than the standard,which has become an important reason for the poor prognosis of elderly patients with malignant tumors.Dietary restriction(DR),which refers to reducing calorie intake while avoiding malnutrition(It is usually common in studies to reduce dietary intake by 30-40%.),is a recognized dietary intervention to delay aging.AimsThe objective of this study was to explore the effects of dietary restriction on the intestinal barrier,infection and survival after chemotherapy in elderly mice.Methods:C57BL/6J young mice(2-3 months)and old mice(20-24 months)were taken,mice were given are fed with AL diet(Ad libitum)or DR diet(Dietary restriction was given 2 weeks before chemotherapy,and the daily amount of food given was 70%of the daily intake of the control mice),and the doses of fluorouracil intraperitoneally in young mice and old mice were 50 mg/kg/d and 40mg/kg/d,for 5 days.The survival rate and weight changes of mice after 5-FU chemotherapy were recorded,and the diarrhea and intestinal histology changes of mice were observed.On the 3rd day after chemotherapy,the small intestine samples of surviving mice were sectioned,and histological anale spleen and liver of mice were collected,and bacterial culture was performed after grinding to study the translocation of intestinal flora.C57BL/6J young mice(2-3 months)were given a AL or DR for 2 weeks,Gastric broad-spectrum antibiotics are then given for 5 days,after which antibiotic-containing drinking water is continued.The control group and the experimental group were injected intraperitoneally with 5-Fu,50 mg/kg/d,after the end of antibiotic gastric feeding,for 5 consecutive days.The survival rate and weight changes of mice after 5-FU chemotherapy were recorded,and intestinal histology changes of mice were observed.On the 3rd day after chemotherapy,the small intestine samples of surviving mice were sectioned,and histological analysis by HE staining,intestinal stem cell counting by immunohistochemical staining.The above experimental methods were used to study the effect of antibiotics on the intestinal barrier and survival of young mice after chemotherapy.Results:(1):The survival rate of young AL mice was 36.67%,and the survival rate of young DR mice was 86.67%,after chemotherapy.The survival rate in elderly AL mice was 3.33%,and the survival rate in elderly DR mice was 76.67%,after chemotherapy.(2):The intestinal tissue structure of YAL and OAL mice was destroyed,intestinal villi were shed and lost,the expression of intestinal inflammatory genes was increased,the number of crypt stem cells decreased,and the intestinal tissue structure of YDR and ODR mice was intact,intestinal inflammation was inhibited,and the number of crypt stem cells was retained.(3):After chemotherapy,the liver and spleen of mice were cultured with bacteria,all OAL mice and most YAL mice were cultured pathogenic bacteria,mainly including Proteus mirabilis,Pseudomonas aeruginosa,Escherichia coli,etc.,most of the YDR,ODR and a small part of YAL did not culture pathogenic bacteria,a small part of YDR,ODR cultured bacteria,mainly including streptococcus and Bacillus cereus.Conclusions:(1):The above experimental results showed that the chemotherapy tolerance of elderly mice was significantly lower than that of young mice,and short-term diet improved the survival rate of young and old mice after chemotherapy.(2):The causes of death of mice after 5-Fu chemotherapy were closely related to the destruction of intestinal barrier,translocation of intestinal flora,and infection of pathogenic bacteria after entering the blood.(3):Dietary restriction protects young,especially elderly mice after 5-Fu chemotherapy,intestinal damage,destruction of intestinal barrier function and reduction of intestinal flora translocation,thereby reducing infection and death after chemotherapy in mice.