Intervention Effect Of Oyster Peptide On Intestinal Barrier Damage Induced By Cisplatin In Mice

Cisplatin(DDP)is a platinum chemotherapeutic drug,which has the characteristics of broad anticancer spectrum,strong effect,synergistic effect with a variety of antineoplastic drugs and no cross-resistance.It is one of the most commonly used drugs in combined chemotherapy.However,cisplatin can also produce gastrointestinal toxicity,prone to vomiting,diarrhea and other adverse reactions,affecting the quality of life of patients and limiting its clinical application.Studies have shown that cisplatin can cause damage to the intestinal barrier.Our previous experiments found that cisplatin can not only cause intestinal damage in mice,but also lead to the decrease of thymus index and immunosuppression in mice.Therefore,it is of great clinical significance to find safe and non-toxic natural products to reduce the toxic and side effects of cisplatin chemotherapeutic drugs.Because of its unique growth environment,marine organisms will produce substances with specific structure and function,which is an important source of natural products.Oysters are one of them.Oyster is one of the first health therapeutic products with the same origin of medicine and food by the health department in China.Some studies have shown that oyster bioactive peptides have the biological function of regulating immunity.The intestinal Barrier damage model of mice was made by cisplatin,oyster peptide was prepared and intervened in mice to explore whether oyster peptide could alleviate the intestinal Barrier damage induced by cisplatin through immunomodulatory effect.Objectives:To determine the intervention effect of oyster peptide on intestinal Barrier damage in mice,and to verify the correlation between the immunomodulatory effect of oyster peptide and the repair of intestinal Barrier damage,so as to provide experimental basis for the clinical application of oyster peptide.Methods:1.Oyster peptides were prepared by trypsin hydrolysis,and the concentration of oyster peptides was determined by biuret method.2.BALB/c mice,male,were randomly divided into three groups: normal control group(Control),cisplatin group(DDP),cisplatin and oyster peptide group(DDP+PEP).DDP+PEP group received intragastric administration of peptide 800mg/kg/day.One hour after the first intragastric administration,cisplatin was injected intraperitoneally in DDP group and DDP+PEP group with a dose of 5mg/kg,and the other groups were injected with the same amount of normal saline.Weigh the mice every day.After seven days of intragastric administration,feces were collected,blood was taken,and the tissues were taken after the mice were killed.3.The thymus and spleen of mice were stripped and the organ index was calculated.The immune factors in serum and intestinal tissue of mice were detected by ELISA method,the intestinal Barrier damage of mice was determined by hematoxylin-eosin staining,a number of indexes of each intestinal barrier of mice were detected by immunohistochemical method,and the 16 s r RNA gene fragments of intestinal flora of mice were sequenced to explore the difference of intestinal microflora diversity among different groups.Results:1.Cisplatin decreased the body weight,organ index and the expression of immune factors in serum and small intestine of mice.After the intervention of oyster peptides,the weight loss of mice decreased,the indexes of thymus and spleen increased,and the contents of immune factors in serum and small intestine increased.2.Cisplatin caused the exfoliation of intestinal epithelial cells,the decrease of tight junction related protein expression,the damage of mechanical barrier and the decrease of mucin expression in chemical barrier.Oyster peptide intervention can alleviate the damage of intestinal barrier induced by cisplatin.3.Cisplatin increased the diversity of intestinal flora and changed the structure of intestinal bacteria in mice,and the proportion of probiotics increased significantly after the intervention of oyster peptides.Conclusions:1.Oyster peptide intervention can reduce the damage of intestinal barrier in mice caused by cisplatin.2.Oyster peptide can regulate the immune function of mice and promote the restoration of intestinal flora,laying the foundation for repairing the normal intestinal barrier.