Study On Effects Of 10-week Swimming Exercise On Food-borne AGEs-induced Liver Injury And RAGE/p38MAPK/NF-κB Pathway In Mice

Research Objective: advanced glycation end products(AGEs)are a class of stable products formed after non-enzymatic glycation reactions.Excessive accumulation of AGEs in the body will induce inflammation and oxidative stress in the body.AGEs-induced inflammation and oxidative stress are closely associated with diabetes,aging,liver disease and complications.In recent years,the study of inhibition of AGEs-induced oxidative stress and inflammation has become a research hotspot,and exercise,as an effective and healthy means,has also attracted much attention to the inhibition of AGEs and the inhibitory effect of AGEs-induced inflammation and oxidative stress.Based on this,this paper comprehensively investigated the effects of regular 10-week swimming exercise on the oxidative stress,inflammation and RAGE(receptor of advanced glycation end products)p38MAPK(p38-mitogen activated protein kinase(p38-MAPK)/NF-κB(nuclear factor-kappa B)pathway in the liver tissue induced by food-derived AGEs in a mouse model.This study aims to provide a scientific basis for exercise to relieve AGEs-induced oxidative stress and inflammation.Research objects and methods: It was divided into two dimensions: body weight,organ index,liver H&E staining,the contents of AGEs in liver,the levels of ROS(reactive oxygen species,reactive oxygen species,ROS)in liver,the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in livers were used to analyze the effects of regular exercise on liver tissue damage in high AGEs-intaked mice.The expression of RAGE/p38MAPK/NF-κB signaling pathway protein was used to analyze the possible mechanism of regular exercise alleviating liver tissue injury in high AGEsintaked mice.Twenty-one male KM mice were randomly divided into normal diet group(group C),exercise high AGEs diet group(group E-A)and high AGEs diet group(group H-A).Only group E-A was subjected to swimming intervention for 10 weeks,six times a week.Each intervention lasted for 10 min in the first week,20 min in the second week,30 minutes in the third week,and 30 min thereafter.Group C was fed normal diet,and E-A and H-A were fed diets of high AGEs.At the end of the experiment,the mice were killed and dissected to take blood and liver tissue.The body weight and organ index of mice were detected.The fluorescent AGEs of feed were determined by fluorescence spectrometry and the degree of Maillard reaction of feed was determined by ultraviolet spectroscopy.After formalin fixation,the liver tissues were embedded with paraffin wax,sliced and stained by H&E,and the pathological morphological changes of the liver tissues were observed and analyzed by light microscopy.Fluorescence AGEs in liver were determined by fluorescence spectrometry.ROS content in liver was determined with ROS kit.RAGE,p38 MAPK,NF-κB,TNF-α and IL-6 levels of expression were measured and compared by immunohistochemistry,and their changes were observed and analyzed.Results:1.AIN-93 G feed was baked at 160°C for 90 min,and the content of fluorescent AGEs in the feed after baking was significantly higher than that in the unbaked feed(P<0.01).2.After 10 weeks of experimental intervention,liver organ index of group H-A was significantly increased compared with group C(P<0.01);Compared with H-A group,the liver organ index of E-A group was significantly decreased(P<0.05).3.H&E staining results showed that after 10 weeks of experimental intervention,compared with group C,the number of inflammatory cell infiltration and steatosis in the liver tissue of group H-A was significantly increased;Compared with H-A group,the number of inflammatory cell infiltration and steatosis decreased in E-A group.4.The results of fluorescent AGEs showed that after 10 weeks of experimental intervention,the content of fluorescent AGEs in the liver tissue of mice in group H-A was significantly increased compared with group C(P<0.01).Compared with H-A group,the content of AGEs in liver tissue of E-A group was significantly decreased(P<0.01).5.Immunohistochemical results showed that after 10 weeks of experimental intervention,the expressions of RAGE,p38 MAPK,NF-κB,TNF-α and IL-6 in the liver tissue of group H-A were significantly increased compared with group C(P<0.01).Compared with H-A group,the expressions of RAGE,p38 MAPK,NF-κB,TNF-α(P<0.01)and IL-6(P<0.05)levels in liver tissue of E-A group were significantly decreased.6.Fluorescent ROS results showed that after 10 weeks of exercise intervention,ROS expression in liver tissue of mice in group H-A was significantly increased compared with group C(P<0.01).Compared with H-A group,ROS expression in liver tissue of E-A group was significantly decreased(P<0.01).Conclusions:1.Regular exercise reduced the content of AGEs in liver of mice with high dietary AGEs.2.Regular exercise alleviated liver tissue damage in mice of AGEs with high diet.3.Regular exercise reduced the expression of RAGE,p38 MAPK and NF-κB levels in liver of mice of high dietary AGEs.4.Regular exercise reduced the generation and accumulation of AGEs in liver.In addition,specific binding between AGEs and RAGE was decreased,inhibiting the activation of RAGE/p38MAPK/NF-κB signaling pathway,reducing the oxidative stress and inflammation response,and thus alleviating tissue damage.