The Effect Of High-glucose Diet On The Redox Status Of Digestive System In Mice And The Underlying Mechanism

Many researches showed the intake of high sugar diet was related to multiple diseases. But the underlying mechanism is still nof fully clear. Oxidative stress is a well-recognized mechanism in many pathological conditions. Digestion, absorption and metabolism in digestive system involve many energy processes which usually accompanied by the production of reactive oxygen species (ROS). Many research reported oxidative stress played important roles in many diseases in digestive system. However there are few researches on the effect of high sugar diet on digestive system and underlying mechanism. In this research, we explored the effect of high glucose diet on digestive system and underlying mechanism, the relation between oxidative and dyslipidemia, which provided the reference value for the prevention and treatment of diseases related to nutrition.Chemiluminescence assay is generally applied to detect ROS in cells or monolayer tissues. There are few assays for detection of ROS in multilayer tissues. We established the chemiluminescence assay for ROS in multilayer tissues with hydrogen peroxide as standard, luminol as probe, horseradish peroxidase as catalyst. We did intragastric administration in Kunming mice, detected the blood glucose concentration and ROS level at different times. The results showed positive correlation between blood glucose concentration and ROS.Mice were fed by diet with different concentration of glucose which were obtained by adjusting the proportion of corn starch and glucose (40%,0;30%,10%;25%,15%;20%, 20%;10%,40%;0,40%). After two weeks, we detected redox status and somatostatin level of blood, stomach, duodenum, jejunum, liver and pancreas in six groups of mice. The results didn't show the correlation between the concentration of glucose and degree of oxidative stress. Diet with 20% glucose induced the optional redox status in duodenum and jejunum. Diet with 40% glucose induced the complete oxidative stress in blood and digestive system. The correlation analysis for somatostatin and ROS suggested somatostatin played important roles in defense against oxidative stress, while ROS was as signal molecule.Why small intestine could defend against oxidative stress induced by high glucose diet (containing 20% glucose)? We did DNA chip using jejunum of mice on high glucose diet for four weeks, comprehensively analyzed genes related to oxidoreductase, found Prdxl and Prdx4 had higher expressions in group fed with high glucose diet compared with control, which suggested Prdxl and Prdx4 played strong roles in defense against oxidative stress in jejunum. We separately detected the relative expression of Prdxl and Prdx4 in mice on diet with different concentration of glucose for two weeks or diet with 20% glucose for four weeks, found the positive correlation between somatotain and the gene expressions of Prdxl and Prdx4. Sum up the above the results, we concluded that ROS as signal molecule induced the secretion of somatostatin, and then somatostain play its roles in defense against oxidative stress by regulating the expressions of Prdxl and Prdx4.We also did DNA chip using liver of mice on high glucose diet for four weeks, comprehensively genes related to ROS production and removing, found that ROS in oxidative stress induced by high GI diet were mainly fromβ-andωoxidation in peroxisome and CYPE1 in microsome, which was different from other researches; high glucose diet impaired the antioxidant defense by down-regulating the expression of genes related to thiol redox.Excess of sugar intake can induce dyslipidemia, whose initiation and development involve oxidative stress. The research on the underlying molecular mechanism of simple sugar inducing deleterious effects on lipid metabolism focused the hepatic gene expression and enzyme activities change related to lipid metabolism. However, there are few researches on the effect of high carbohydrate on lipid metabolism of intestine. In this research, we fed mice with high glucose diet (containing 20% glucose) for four weeks, detected the effect of high glucose diet on blood lipid profiles. The results showed high glucose diet feeding induced dyslipidemia in mice. In order to explore the mechanism of dyslipidemia induced by high glucose diet, we comprehensively analyzed expressions of genes related to lipid metabolism in liver and jejunum using microarray analysis, found expressions of genes related to triglyceride hydrolysis and fatty acid oxidation in peroxisome were different from control. Fatty oxidation in peroxisome was accompanied by the production of ROS, which verified that oxidative stress participated in the initiation and development of dyslipidemia. Microarray analysis for jejunum showed the intake of high glucose diet influenced expressions of genes related to triglyceride digestion, absorption and deposit. The expressions of genes related to lipid metabolism in liver and jejunum, together with oxidative stress, participated in the initiation and development of dyslipidemia induced by high glucose diet.