The Effects Of Aerobic Exercise On The Intestinal Tumors And Flora Of The Apc^Min/+Mouse Model

Objective:To explore the effects of aerobic exercise on intestinal growth and flora in Apc^Min/+mice,and try to find the possible correlation between changes in intestinal flora and tumor growth after aerobic exercise intervention.Methods:The Apc^Min/+mouse model is a widely accepted animal model that can spontaneously form multiple intestinal neoplasias.And is mainly used to reseach measures to prevent the occurrence and development of colorectal tumors.And our study is based on this model:1.Reproduction identification and intervention:18 required Apc^Min/+mice were selected through reproduction identification.Experimental mice were completely randomly divided into model control group,aerobic exercise group and aspirin positive control group according to a random number table,and C57BL/6J wild type mice were used as blank control group.The aerobic exercise group was subjected to moderate-intensity aerobic exercise?12m/s,60min/d,5d/w?for 12 weeks;while the mice of the other three groups were placed in the cage for free movement;Meanwile,the Aspirin group was continuously savored with aspirin for 12 weeks.2.Weight scale and tumor numbers:All the mice were weighed and mice body weight recorded every week.All experimental mice were executed and dissected after the experimental intervention,and the intestinal tissues of the mice were taken to count the number of adenomas.3.Histopathology,cell proliferation,apoptosis and protein expression:TUNEL immunofluorescence technique was used to detect the effects of aerobic exercise on apoptosis of intestinal tumor cells.HE staining and IHC were used to detect the effects of aerobic exercise on the expression of downstream proteins of Wnt signaling pathway?C-Myc?and cell proliferation?Ki-67?in the intestinal tumor cells.Simultaneously.4.Flora sequencing and analysis:The intestinal flora:16S rRNA sequencing on the intestinal feces of each group of mice was used to analyze and compare the composition and diversity of intestinal flora before and after 12-week experimental intervention to look for the effect of aerobic exercise on the intestinal flora of Apc^Min/+mice was observed.Results:1.Reproduction identification:Apc^Min/+male mouse model that meets the experimental needs was successfully screened through the breeding and genetic identification.General signs:As the age of mice increasing,hair loss,white nails,prolapse,bloody stools,increased facial secretions,decreased vitality and other symptoms were gradually observed in model group mice,together with the subcutaneous or mammary gland tumors.In comparison,general signs of the aerobic exercise group and Aspirin group were better than that of the model control group.2.Weight change:After 12 weeks of experiment,the body weight change rate of the blank control group and the aspirin group was 15.2%and17.5%higher than that of the model control group?P<0.01?,and the body weight change rate of the aerobic exercise group was 8.6%higher than that of the model control group?P<0.05?.The number of tumors:Compared with the model control group,the aerobic exercise group and the aspirin group could inhibit the occurrence of intestinal tumors,and the inhibition rates were 40.93%?P<0.05?and 65.89%?P<0.01?,respectively.3.Cell proliferation:Compared with the model control group,the apoptotic cells in the aerobic exercise group were significantly increased 8.3%by TUNEL staining,and the difference was statistically significant?P<0.05?.HE staining:Compared with the model group,intestinal tumors in the aerobic exercise group and the aspirin group are mainly adenomas after HE staining:mainly low-grade tumor adenomas,and some high-grade tumors;while glands tumors are mainly high-grade tumors in the model group,and cancers appear in individual glands tumors.IHC:The results of IHC showed that the expressions of c-Myc and Ki-67 in the aerobic exercise group and the aspirin group had no differences.Flora sequencing and analysis:Aerobic exercise has a regulatory effect on the abundance of some genus?16/149?in the gut microbiota?P<0.01?,such as increasing the abundance of some probiotics represented by Ruminococcaceae?ruminal bacteria?and reducing The abundance of some pathogenic bacteria represented by Escherichia-Shigella?Shigella?.Conclusion:Aerobic exercise has a good preventive effect on intestinal tumors of Apc^Min/+mice,which can inhibit the occurrence of tumors?adenomas?by inducing apoptosis of intestinal tumor cells and inhibiting the number of intestinal tumors.Meanwhile,aerobic exercise has a regulating effect on the abundance of some bacteria in the gut genus,which can affect the intestinal flora by increasing the abundance of probiotics and reducing the abundance of pathogenic bacteria.The number of intestinal tumors in Apc^Min/+mice was correlated with the abundance of some species in the intestinal flora?positive correlation with probiotic abundance and negative correlation with conditional pathogen abundance?.The change in abundance of the flora may be one of the reasons by which aerobic exercise regulates the number of intestinal tumors.