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Expression And Significance Of 11-β Hydroxysteroid Dehydrogenase Type 1 In Rat Model With Metabolic Syndrome

Posted on:2009-01-13Degree:MasterType:Thesis
Country:ChinaCandidate:Y F ShiFull Text:PDF
GTID:2144360242980235Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
At present the metabolic syndrome HPA axis stress hypothesis is not yet clear, and elevated cortisol levels in patients with metabolic syndrome are not necessarily, some studies found that the cortisol levels in metabolic syndrome patients were lower than the control group, and further research found that local tissue glucocorticoid levels in patients with metabolism syndrome increased, and it suggested that the expression and activity of the key enzyme (11β-HSD1) participating in glucocorticoid metabolism and regulation increased, leading to the increased local tissue glucocorticoid levels. The introduction of stress in metabolic syndrome model making on the basis of high-calorie, high-salt diet was made in this study, and we had established a general dietary control group, high-calorie, high-salt diet group, the stress + high-calorie, high-salt diet group, the stress + general dietary group. Through the evaluation and analysis of stress in the process of making a model, and observing effects to characteristics of the MS including blood pressure, blood lipids, obesity, blood glucose, insulin resistance, we intended to verify the metabolic syndrome HPA axis stress hypothesis. At the same time we observed the 11β-HSD1 mRNA levels in every group to evaluate the expression and significance of 11β-HSD1 in the groups mentioned above.Objective: To investigate the stress factors in the rat model of metabolic syndrome and the role and significance of 11-βhydroxysteroid dehydrogenase type 1 in a rat model of metabolic syndrome. Methods: 40 Male 2-month-old Wistar rats were randomly divided into four groups:A for general dietary control group (N = 10);B for high-calorie, high-salt diet group (N = 10);C for stress + high-calorie, high-salt diet group (N = 10);D for stress + general dietary group (N = 10). Food intake, body weight and blood pressure in Group A and Group C were measured one time every week, while body weight and blood pressure were in statistical significance using independent samples t-test statistical analysis, references of model making period in literature were made, then the date of termination was chosen. Fasting for 12 hours, tail vein blood were obtained, fasting blood glucose, triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL-C), low density lipoprotein cholesterol (LDL-C) were measured using automatic biochemical analyzer, adrenocorticotropic hormone (ACTH) levels in each group were tested by enzyme-linked immunosorbent assay test ,then statistical analysis of the data were made, and rats were sacrificed autopsy, fat tissue was collected for testing expression of 11β-HSD1mRNA by RT-PCR.Results: (1) the Group B, C and Group D's consumption volume significantly decreased after one week compared with group A with statistically significant difference (P <0.01), Group B and Group C continued into the first three weeks in this situation. Group D's appetites gradually restored after two weeks, Group B and Group C's consumption had increased compared with the control group significantly at the fifth week, sixth week, seventh week, eighth week, and had a statistically significant difference (P <0.01). Group D's consumption had increased com pared with the control group statistically significantl at the eighth week (P <0.01). The consumption of Group B, C and D increased compared with the control group at the eighth week, a statistically significant difference, while Group C compared with Group B , group C compared with group D both had statistically significant difference (P <0.01). (2) Group B and Group C started increasing weight at the fourth week and continued to the eighth week , the diffreences between anyone of them and the control group showed a statistically significant difference (P <0.01), Group B and Group C had no statistically significant differences. The differences between Group B and Group D, Group C and Group D were statistically significant (P <0.01) at thefourth week in weight. While Group D was compared with the control group, there was no statistically significant difference at 1-6 week, there were statistically differences at 7-8 week (P <0.01). (3) When Group B's blood pressure was compared with the control group, there was no statistically significant difference. Group C had higher blood pressure than those in the control group at 3-8 week, a significant statistically difference (p <0.01). And Group C had higher blood pressure than Group B statistically significant (p <0.01) at the eighth week. The differences between Group D and Group A were statistically significant (p <0.01) at 4-8 week. (4) Group B in the TC, TG, VLDL, LDL and HDL levels were higher than those in the control group, which were statistically significant (p <0.01). Group C in TC, TG, VLDL, LDL, HDL, FPG levels were higher than the control group, which were statistically significant (p <0.01), and group C in VLDL, LDL, FPG levels were higher than in Group B, which were sta tistically significant (p <0.01). Group C in VLDL, LDL, FPG levels were higher than Group D , which were statistically significant (p <0.01). When Group D was compared with the control group in the blood lipids and glucose levels, there was no statistical difference. (5) Blood glucose levels were tested at 0, 0.5, 1 and 2 hour after gavage to rats with glucose, Group B, Group C and Group D's blood glucose values were higher than those in the control group, with statistically significant difference (p <0.01). It showd that the three groups were subject to impaired glucose tolerance, when Group C was compared with Group D in blood glucose levels at 0, 0.5, 1 and 2 hour after gavage, there were still statistically significant differences. When Group C was compared with Group B in blood glucose levels at 1 and 2 hour after gavage, there were still statistically significant differences.The data above indicated that the three groups were subject to varying degrees of injury impaired glucose tolerance, insulin resistance might existed.(6) The levels of adrenocorticotropic hormone (ACTH) in Group C and Group D were higher than the control group A statistically significant (p<0.01). Group C and Group D were in state of stress. (7) The levels of 11β-HSD1 mRNA in GroupB, C, D were statistically significant different to the control group A (p <0.01), and differences between Group C and Group B ,Group C and Group D were statistically significant (p <0.01). Group B and Group D had no statistically significant difference.Conclusion: (1) In the process of model making of metabolic syndrome, stress alone can cause weight gain, insulin resistance, and high blood pressure, blood lipids levels were less affected, but stress and hig h-calorie, high-salt diet in weight gain, insulin resistance, elevated blood lipids had synergies. Stress had significant advantages in high blood pressure in the model making. (2) The expression of 11β-HSD-1 increased in group high-calorie, high-salt diet, stress and stress + high-calorie, high-salt diet group. Stress + high-calorie, high-salt diet group increased significantly, the two factors had synergies, 11β-HSD1 might be the important factor in the metabolic syndrome.The results showed that: stress could cause weight gain, insulin resistance, blood pressure, but blood glucose and lipids were less affected, stress and high-calorie, high-salt diet in weight gain, insulin resistance, elevated blood lipids had synergies. Stress had significant advantages in high blood pressure in the model making. The experiment tested the metabolic syndrome HPA axis stress hypothesis, stress and high-calorie, high-salt diet combined with the modern way of life, there could be all kinds of metabolic syndrome characterized at the same time .The increasing 11β- HSD1 expression in the models of metabolic syndrome might contribute more in etiology of metabolic syndrome and the studies provided a experimental basis for treatment of 11β-HSD1 inhibitor in metabolic syndrome...
Keywords/Search Tags:metabolic syndrome, 11-βhydroxysteroid dehydrogenase type 1, model, stress, rat
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