Effect Of Chitooligosaccharide On Alcoholic Intestinal Injury In Rats

Alcohol-related illnesses and health problems,especially alcoholic liver damage,have been getting a lot of attention,and many of these injuries are linked to the health of the intestinal barrier.Alcohol can damage the intestinal barrier by destroying the mucosal structure,oxidative stress and inflammatory response,and allow harmful substances to enter the body,thereby damaging organs and tissues.As a kind of natural alkaline oligomer,chitooligosaccharide(COS)has catched more and more attention due to its wide sources,non-toxic,easy biodegradation and physiological activities such as relieving alcohol and protecting liver.In this study,the intervention effect of COS on alcoholic intestinal injury in rats was investigated,so as to provide theoretical support for the development of the function of COS and the development of safe and effective intestinal protective products.The main research contents and results of this study are as follows:(1)The intestinal damage model was established by intragastric alcohol treatment for 42 days in Wistar rats.Before intragastric alcohol treatment,180 mg/kg glutamine,22.5 mg/kg,45 mg/kg and 90 mg/kg COS were administered respectively.The growth status,small intestine elasticity and morphology of rats were analyzed by the weight,food intake,organ index,and the weight/length ratio and histopathological examination of small intestine.The results showed that alcohol had more serious damage to the duodenum in the small intestine than jejunum and ileum.COS could increase the weight of rats,reduce the organ damage caused by alcohol,improve the changes of duodenum and ileum elasticity after alcohol consumption,and reduce the intestinal discomfort of rats.At the same time,the ratio of villi length to recess depth was increased by maintaining villi morphology,increasing villi length,and decreasing muscle thickness,so as to alleviate the damage of alcohol to the structure and function of small intestine in rats.(2)The protection of COS on intestinal mucosal barrier was investigated in the model of alcoholic intestinal injury in rats.It was investigated by measuring the contents of D-lactic acid(D-LA),Di-amine oxidase(DAO)and Lipopolysaccharide(LPS)in the plasma,as well as the expression of proteins related to tight junction structure.The results showed that the intervention of COS could significantly reduce the content of D-LA,LPS and the DAO activity in plasma of rats,and reduce the increase of intestinal mucosal permeability caused by alcohol.COS could increase the gene and protein expression of Occludin and ZO-1,reduce the gene and protein expression of Claudin-4,and repair the tight junctions between the small intestinal epithelial cells.(3)The effect of COS on oxidative stress in small intestine was investigated in the model of alcoholic intestinal injury in rats.The total antioxidant capacity and activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)of small intestine were measured to detect the ability of the small intestine to prevent oxidative stress.The oxidative damage of the small intestine was characterized by the content of malondialdehyde(MDA)and protein carbonyl.The results showed that COS intake could improve the total antioxidant capacity of small intestine tissues,significantly increase the activity of SOD and GSH-Px of small intestine tissues,significantly reduce the content of MDA and protein carbonyl in small intestine,and alleviate the oxidative damage of small intestine caused by gavage alcohol.(4)The intervention effect of COS on inflammatory response were discussed in the model of alcoholic intestinal injury in rats.The anti-inflammatory level of COS was studied by measuring the content of pro-inflammatory factors in the plasma of rats.The regulation effect of COS on intestinal inflammation was investigated by measuring the content of NO and iNOS activity in the small intestine,as well as the mRNA and protein expression of pro-inflammatory and upstream factors.The results showed that COS could alleviate the inflammation of the whole body by downning the plasma levels of IL-6,IL-1β and TNF-α.In addition,COS could down-regulate the expressions of mRNA of IL-6,IL-1β and TNF-α,and reduce the content of NO in the small intestinal tissues by decreasing the activity of iNOS,so as to alleviate intestinal inflammation.COS reduced the mRNA expressions of TLR4,TLR2,and TRAF6,as well as the protein expressions of TLR4 and nuclear phosphorylated NF-κB p65,suggesting that COS might play a protective role in the inflammatory response of the small intestine by regulating the inhibition of TLR4 protein expression and the activation of NF-κB pathway.