The Effect Of Heme On Colitis-Associated Colorectal Cancer In Mice

Edible meat has important effects on the organism,by providing nutrients such as essential amino acids,vitamins and minerals.Red meat is processed(being pickled or added chemical preservatives and additives,etc.)to prolong its shelf life or improve its flavor.In recent decades,global consumption of red meat has been increasing,especially in developing countries.At the same time,there is growing evidence that intaking a large amount of red meat,especially processed meat,may increase the risk of several major chronic diseases.Epidemiological studies have revealed that excessive intake of red meat can significantly increase the risk of colorectal cancer,but the exact mechanism has not been clarified.Heme is one of the main components of red meat,which may play a certain role in the risk of colorectal cancer.We will investigate its influence on the onset and progression of ulcerative colitis-related colorectal tumors and its possible mechanism.Therefore,this thesis will take heme iron as the research object,explore the influence of heme iron intake on the onset and progression of colorectal cancer,and conduct preliminary research and analysis on the possible impact mechanism in the process.The main research contents are as follows:First,in five-week-old C57BL/6N male mice,ulcerative colitis-related colorectal tumors in mice induced by Azoxymethane /Dextran sulfate sodium salt were established Model to explore the effect of heme iron on the occurrence and development of colorectal tumors in mice,and analyze the effect of heme iron on the weight of mice and the number of colorectal tumors.Under the condition that the dosage of heme iron used has no obvious abnormal response to mice,the results of animal experiments show that compared with the model group,the intervention of heme iron can increase the occurrence and development of colorectal tumors.During the feeding period The degree of blood in the stool and diarrhea is more serious,and it can significantly increase the level of oxidative stress indicator myeloperoxidase MPO activity and lipid peroxide LPO content in the mouse colon tissue.By measuring the level of inflammation in the mouse colon tissue,it is found Under the intervention of heme iron,it can slightly increase the levels of cytoinflammatory factors interleukin-6 and tumor necrosis factor-? in the colon tissue of mice.By measuring the plasma lipopolysaccharide(LPS)content,it is found to be up-regulated.The intestinal permeability of the mouse colon has also been improved to a certain extent.Later,Western blotting and immunohistochemistry were used to explore the possible influence mechanisms.The results show that compared with the model group,under the intervention of heme iron,the expression of xanthine oxidase XO in the colon can be significantly increased,and the expressions of p-H2 AX and p-STAT3 are up-regulated to a certain extent,and the expression of XO is up-regulated.It may promote the imbalance of oxidative stress.The up-regulation of p-H2 AX and P-stat3 indicates that DNA damage is caused in mouse colon tissue and the level of carcinogenesis is increased.In order to further locate the possible expression site of XO,immunohistochemical method was used to locate XO where the expression site and the macrophage site are highly overlapped,which indicates that XO may be derived from macrophages,and the increase in plasma LPS content may be caused by LPS stimulation.After the macrophages are exposed to iron,XO is expressed.Finally,establish an in vitro cell model,use THP-1 as the experimental object,and induce THP-1 cells to differentiate into macrophages through phorbol12-myristate13-acetate(PMA).Then lipopolysaccharide at an appropriate concentration stimulates the macrophages to activate them,and then the macrophages are stimulated with sucrose iron at an appropriate concentration.It is found that the cells induced to differentiate in this case will express xanthine oxidase,and There is a dose-dependent phenomenon,that is,the higher the concentration of iron sucrose,the more xanthine oxidase is expressed.In summary,this study proves to a certain extent that heme can increase the number of colorectal tumors in the mouse model of ulcerative colitis-related colorectal tumors,aggravate the degree of tumor development,and increase the level of oxidative stress in colon tissues,and tumor tissues The expression level is more obvious than that in adjacent tissues.It is believed that this phenomenon may be related to the up-regulation of XO expression,and XO is most likely to come from colonic macrophages.This study provides a certain reference for the red meat intake to increase the risk of colorectal cancer,and provides a certain warning effect.