Preliminary Study On Intestinal Injury Induced By Lactic Acid Bacteria Interfering With Chemotherapy Drugs

Normal small intestine epithelial tissue is highly sensitive to chemotherapy drugs and is the main site of injury during chemotherapy.This injury is also the main limiting factor for the dose of chemotherapy treatment for rectal cancer and abdominal malignant tumors.In literature reports,lactic acid bacteria are generally believed to protect the intestinal mucosa from loss and regulate the body's immune response.They are made into yogurt for daily drinking.They have also been widely used as microecological preparations in clinical treatment of diseases such as diarrhea.There are few literature reports on the effectiveness and safety issues.Therefore,this paper explores the interference effect of lactic acid strains and the molecular mechanism through the animal model of chemotherapy,and hopes to provide data support for the clinical use of lactic acid bacteria for interference chemotherapy.First of all,87 strains of lactic acid bacteria stored in the laboratory were selected and screened with the aid of H2O2 induced oxidative damage cell model of Caco-2 cells,and then verified by isolated small intestine tissue and animal models.The results showed that among the 87 strains of lactic acid bacteria,28 strains could significantly down-regulate the LDH leakage status of Caco-2 cells caused by H2O2,and it is particularly noteworthy that Lactobacillus rhamnosus FLRH93 had the lowest down-regulation of LDH(about the model group)53%).Compared with the leakage status of the isolated small intestine tissue of the blank control group,Lactobacillus rhamnosus FLRH93 can significantly reduce the permeability of the small intestine.With the help of transcriptomics sequencing,the effect of Lactobacillus rhamnosus FLRH93 on the transcription level of Caco-2 cells was detected and found(how many genes were up-regulated and how many were down-regulated).Further,by constructing 5-fluorouracil(5-FU)-induced mouse intestinal injury model,the repair effect of Lactobacillus rhamnosus FLRH93 was verified.Analysis of daily body weight and food intake changes,intestinal blue glucan leakage,HE staining and AB-PAS staining intestinal histopathological changes,and serum IL1-? and TNF-?,through immune tissue The expression levels of Bcl-2 and NLRP3 in intestinal tissue were detected by chemical staining,real-time fluorescence quantitative PCR and Western blotting.The results confirmed that Lactobacillus rhamnosus FLRH93 fermented milk can significantly improve the intestinal damage caused by 5-FU.HE staining and AB-PAS staining sections showed that the strain maintained the integrity of the microstructure of the small intestine,reduced goblet cell loss after 5-FU treatment,and up-regulated the expression of Bcl-2 and down-regulated NLRP3 in the injured mouse intestine.Secretion,thereby reducing the production of inflammatory factors IL1-? and TNF-?in the serum.In the survival experiment of mice injected with 5-FU continuously,the survival rate of mice after intervention with Lactobacillus rhamnosus FLRH93 fermented milk was twice that of the model group.In order to further understand the effect of lactic acid bacteria on intestinal injury induced by chemotherapy,we used doxorubicin(DOX)-induced intestinal injury as a model for verification,and selected Lactobacillus rhamnosus FLRH93 and Lactobacillus planta rum FLPL132 for intervention.Explore lactic acid bacteria through the changes of mouse body weight,survival rate,intestinal appearance and morphology,small intestine HE staining and AB-PAS staining,the expression of IL-6 and TNF-? in the serum,and the expression of NF-?B and MCP-1 in the intestine Interfering effects on chemotherapy injury repair.The results showed that in the DOX-induced injury model,Lactobacillus rhamnosus was not protective,and Lactobacillus plantarum FLPL132 showed significant side effects,up-regulated the expression of inflammatory factors IL-6 and TNF-? in the serum and The expression levels of NF-?B and MCP-1 in the intestine aggravated the intestinal damage of mice,reduced the survival rate of chemotherapy mice,and increased the occurrence of small intestinal swelling in chemotherapy mice.The above research shows that Lactobacillus rhamnosus FLRH93 has a good repair effect on 5-FU-induced intestinal injury,but has no significant effect on DOX-induced intestinal injury,while Lactobacillus plantarum FLPL132 in DOX-induced intestinal injury The tract injury intervention has adverse reactions that promote intestinal obstruction.For the treatment of intestinal injury induced by lactic acid bacteria interference chemotherapy,the influence of strain type,chemotherapy regimen and other potential factors should be fully considered.This study has confirmed for the first time through experiments that lactic acid bacteria interfere with chemotherapy-induced damage with toxic and side effects,breaking people's understanding of the safety of probiotics across the board.