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The Research Of Sodium Tungstate On The Improving Effect And Mechanism In Sodium Glutamate Induced Metabolic Syndrome Mice

Posted on:2016-09-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y T WangFull Text:PDF
GTID:2284330461462791Subject:Pharmacology
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Objective: The study of sodium tungstate on glutamate induced metabolic syndrome(obesity) preliminary study of effect and mechanism of mice.Method:Animal experiment: to construct the model of obesity, this experiment on neonatal ICR mice subcutaneous injection of 4g/kg sodium glutamate, feeding to 4-month-old will meet the obesity. Model mice were divided into 6 groups according to body weight: normal group, model group, low dose group(sodium tungstate, 0.3mg/ml in drinking water), sodium tungstate, 0.7mg/ml in drinking water), high dose group(sodium tungstate, 2mg/ml in drinking water) and positive drug group(orlistat 120mg/kg). Detailed record of mice body length, abdominal circumference, body weight change, food intake, water intake was monitored. During the period, fecal fat content were determined in fresh stool, and Lee ’s index was measured before killing animal. After continuous administration for 6 weeks, the rats were killed by decapitation and serum glucose, triglyceride, total cholesterol were measured. All abdominal white adipose tissue weight was weighed, and then part of white adipose tissue and liver tissue was fixed in 4% paraformaldehyde for pathological sections. Pathological section H-E staining in white adipose tissue, liver tissue pathological section was stained by Oil Red O. Liver glucose and lipids were determined, and the expression of adiponectin protein in the white adipose tissue were observed with Western Blot method.Cell experiment: 3T3-LI preadipocytes were cultured in a 6 well culture plate with culture containing 10% fetal bovine serum and high-glucose DMEM for 48 h, and then 0.5mmol/L IBMX, 0.25nmol/L dexamethasone and lmg/L insulin were added into DMEM culture for 48 h. 100, 300, 900 M sodium tungstate were added into culture(and set up the control group) for another 48 h, Oil Red O staining cells, judging the degree of lipid droplets. Another group of cells also processing, adding cell lysate extraction protein, adiponectin protein expression was observed by Western Blot method.Results:1 Effect of sodium tungstate on body weight, waist circumference and Lee’s index in MSG mice: sodium tungstate can inhibit the growth of body weight gain with a dose-dependent manner in MSG mice; middle and high dose of sodium tungstate can significantly reduce abdominal circumference and Lee’s index.2 Effect of sodium tungstate on food intake and water intake in MSG mice:sodium tungstate does not affect food intake and water intake.3 Effect of sodium tungstate on abdominal fat wet weight in MSG mice: sodium tungstate can significantly reduce abdomen white fat wet weight with a dose-dependent relationship in MSG mice.4 Effect of sodium tungstate on serum glucose, total cholesterol and triglyceride in MSG mice: high dose sodium tungstate can significantly lower the blood glucose concentration; middle and high dose of sodium tungstate can significantly reduce serum triglyceride,total cholesterol in MSG mice.5 Effect of sodium tungstate on fecal total cholesterol, triglyceride content in MSG mice: middle and high dose sodium tungstate significantly increased the content of triglyceride in the feces of MSG mice.6. Effect of sodium tungstate on liver glucose, total cholesterol and triglyceride in MSG mice: high dose sodium tungstate can significantly reduce the content of glucose in the liver of MSG mice; middle and high dose sodium tungstate can significantly reduce the content of triglyceride in the liver; high dose of sodium tungstate can significantly reduce total cholesterol content in the liver.7 Effect of sodium tungstate adipose cell size of WAT in MSG mice: middle and high dose of sodium tungstate can significantly reduce fat cell diameter of WAT.8 Effect of sodium tungstate on liver steatosis in MSG mice: middle and high dose of sodium tungstate can significantly improve the fatty liver disease in MSG mice.9 Effect of sodium tungstate on adiponectin expression of WAT in MSG mice: middle and high dose of sodium tungstate could significantly increase the expression of adiponectin of WAT.10 Effect of sodium tungstate on 3T3-L1 cells induced into adipocytes: middle and high dose of sodium tungstate can significantly inhibit the fat accumulation in 3T3-L1 cells.11 Effect of sodium tungstate on adiponectin expression of 3T3-L1 cells induced into adipocytes: middle and high dose could significantly increase adiponectin levels in 3T3-L1 cells.Conclusion:The experimental mice induced by sodium glutamate appear obvious obesity signs, sodium tungstate can reduce body weight and Lee ’s index, and reduce abdominal obesity degree; sodium tungstate play a role in weight loss and does not affect the food intake of animal model; high dose of sodium tungstate can decrease blood and liver glucose level; sodium tungstate can improve hyperlipidemia of MSG obese mice, reduce abdominal white adipose cell diameter, increasing the content of TG in feces. The effect of sodium tungstate may be due to inhibition of fat absorption in the intestinal tract and promote fat cell differentiation into fat storage capacity of more small fat cells; sodium tungstate can reduce the accumulation of TG in the liver, relieving the degree of non alcoholic fatty liver disease in mouse model. In vivo and in vitro, the results from the Western blot suggest that sodium tungstate elevated the levels of adiponectin secreted by adipose cells, suggesting that weight loss, hypoglycemic, lipid-lowering effect and the effects of nonalcoholic fatty liver disease of sodium tungstate, possibly due to regulating the body’s levels of adiponectin. The development and utilization of metabolic syndrome drug treatment based our study may be useful to expand the idea, having greater innovation and application value.
Keywords/Search Tags:Sodium tungstate, monosodium glutamate, mice, weight loss, anti-hyperlipidemic, hypoglycemic, nonalcoholic fatty liver disease, metabolic syndrome, adiponectin
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