Study On The Delayed Effect And Mechanism Of Tanshinone ⅡA On AOM/DSS-induced Inflammation-related Colorectal Cancer Model In Mic

Objective: In this study,a mouse colitis cancer transformation model induced by AOM/DSS was used as the research object.On the basis of clarifying that tanshinone Ⅱ A prevented and delayed inflammatory colon cancer in mice,different doses of tanshinone Ⅱ A were observed on the expression of TNF and Ang-4 in colon tissue of mice,and the mechanism of tanshinone ⅱ A prevention and treatment of inflammatory colon cancer was discussed.Methods:1.The establishment of inflammatory associated intestinal cancer induced by AOM/DSS in mice: This experiment was divided into model group and blank group.The model group was divided into 10mg/Kg group,12.5mg/Kg group and 15mg/Kg group according to the concentration of AOM.On the 0 day of intraperitoneal injection of AOM,2.5%DSS solution was given after 7 days of continuous drinking for 7 days,and then changed to ordinary drinking water for 14 days,with 1 cycle every21 days and 3 cycles respectively.The general condition,diet and weight changes of mice were observed in the experiment.The whole section of colorectal was removed at the end of the 6th,9th,14 th and 18 th week of the experiment,and the general morphology of colon tissue was observed after sampling.HE staining was used to observe the pathological condition of colon tissue and determine the concentration of AOM.2.Study on the inhibition effect and mechanism of tanshinone ⅡA on AOM/DSS induced mouse inflammatory associated colorectal cancer model: Mice were randomly divided into blank group,model group,lowdose tanshinone Ⅱ A group,medium dose tanshinone Ⅱ A group,and high-dose tanshinone Ⅱ A group.Except for blank group,mice in other groups were induced to model by AOM/DSS,and were given corresponding drug intervention starting from the 3rd week of the experiment,and continued to be given until the end of the experiment.The general condition,diet and weight changes of mice were observed in the experiment.The whole section of colorectal was removed at the end of the 6th,9th,14 th and 18 th week of the experiment,and the general morphology of colon tissue was observed after sampling.The pathological condition of colon tissue was observed by HE staining,and the optimum compatibility ratio of fructus officinalis was screened.The expressions of TNF and Ang-4 in colon tissues were detected by real-time quantitative PCR.Results:1.Establishment of a mouse model of inflammatory associated colorectal cancer induced by AOM combined with DSS: After intraperitoneal injection of AOM,the mice generally did not change.After the administration of DSS,the mice in each model group gradually decreased their activities,decreased food intake,weight loss,diarrhea,bloody stools,and even bowed back.HE staining showed that at the end of the6 th week,a small number of inflammatory cells could be seen in the single columnar epithelium and intrinsic base of the colon in most tissues,and the crypt structure was disordered(slight),suggesting the formation of inflammation,a small number of crypt structure was disordered,interstitial inflammatory cells increased significantly,crypt abscess and glandular hyperplasia were observed,and multiple aberrant crypt foci could be seen,showing atypical hyperplasia and nuclear fission.The epithelial cells of the focal gland were increased in layers,the nuclei were slightly large and deeply stained,and some of them showed atypical hyperplasia.At the end of the 9th week,severe atypical hyperplasia of the colon mucosa,distortion of the structure of most of the colon glands,focal atypical glands infiltrating into the mucosal muscle layer,colon tumor formation,and the region showed high-grade intraepithelial neoplasia and canceration.At the end of the 14 th and 18 th week,the incidence of colon tumor was significantly increased.2.TanshinoneⅡ A can reduce the tumor formation rate of inflammatory associated colorectal cancer in mice induced by AOM/DSS and improve the life status of mice.HE staining showed that tanshinone ⅡA medium dose group delayed the time of colorectal cancer formation and reduced the degree of tumor invasion.QPCR showed that tanshinone ⅡA group could reduce the expression of TNF and Ang-4 in colorectal tissues compared with model group(p< 0.05).Conclusion: In the process of AOM combined with DSS induced inflammation related colon cancer model,the medium dose group of tanshinone IIA has the effect of inhibiting the occurrence of intestinal tumors in mice,while improving the general condition of the model mice.Its mechanism of delaying inflammation related colon cancer may be related to reducing TNF and Ang-4 in intestinal tissue.