The Study Of Expression And Significance Of PAI-1and VWF In Young Rats And Children And Adolescents With Metabolic Syndrome

Part1Establishment of the metabolic syndrome model of young rats and detect of endothelial cell dysfunction in the animal modelObjective:To establish the metabolic syndrome model of young rats through eating high salt and fat diet and to detect the expression of the vascular endothelial cell dysfunction markers, PAI-1and vWF, in the abdominal aorta and the blood serum in young rats with metabolic syndrome(MS), therefore to investigate the role and significance of PAI-1and vWF in the endothelial cell dysfunction(ECD). Methods: Thirty-six3-week-old young SD rats were randomly divided into three groups: routine diet (NC), high fat diet (FC), and high fat and salt diet (FSC), every twelve animals were in each group.When the animals were7-week old, the weight, length, abdominal circumference(AC), blood pressure were measured using standard instruments and procedures. The level of cholesterol(TC)、triglyceride(TG)、 high-density lipoprotein(HDL)、fasting plasma glucose(FPG)、fasting insulin(FINS) was measured after fasting for12hours by taking the tail vein. The fat tissue which was come from the perinephric fat was measured after the rats were killed. Statistical methods were used to calculate whether the indexes between the three groups was statistically significant in order to identify if the model of the metabolic syndrome of young rats was established successfully. The abdominal aorta was taken after the model was successfully established, the pathological changes of abdominal aorta were observed by HE staining, and the expression of PAI-1and vWF were detected by immunohistochemistry as well. In addition, the level of PAI-1and vWF in the serum was detected by enzyme-linked immunosorbent assay(ELISA). The expression of PAI-1and vWF in the three groups was copared by statistical analysis inorder to certificate if young rats with MS were complicated by ECD. Results:1.The body weight, abdominal circumference,weight of the fat tissue in the FSC group were higher than those in NC group, the outcome was statistically significant(P<0.05).The level of SBP, DBP, TG, TC, FPG,FINS in the FSC group were all higher than those in NC group, but the HDL was lower, the outcome was statistically significant(P< 0.05). The rats in FSC group had the fetures of MS of children and adolescents.2. The body weight, abdominal circumference, weight of the fat tissue,FPG,FINS in the FC group were higher than the NC group, the outcome was statistically significant(P<0.05), while the blood pressure, blood lipids were not significantly different between the two groups(P>0.05).3. The abdominal aortic endothelial cells were normal and the structure of the vessel wall was complete in the NC and FC group which were observed by microscope. However, the endothelial cells peeled off from the abdominal aorta and muscle cells disorder were found in the FSC group compared to that of other groups.4.The expression of PAI-1and vWF in the abdominal aorta cells was significantly higher in the FSC group than that in other groups (P<0.05),the difference was statistically significant.5. The expression of PAI-1and vWF in the serum was significantly higher in the FSC group than that in other groups (P<0.05),the difference was statistically significant. Conclusion:1.After four weeks feeding by high fat and salt diet, the rats in FSC group showed the characters of obesity, hypertension, high FPG, low HDL, which were similar to the children with metabolic syndrome in clinical, so the model of metabolic syndrome in young rats was successfully established. After four weeks feeding by high fat diet, the rats in FC group only showed the characters of fat and high FPG,high FINS,did not show the characters of hypertension, low HDL,etc.2. The expression of PAI-1and vWF in the abdominal aorta cells and in the blood was significantly higher in the FSC group, so endothelial cell dysfunction is correlated with metabolic syndrome in the young rat model. While the expression of PAI-1and vWF in the abdominal aorta cells and in the blood in FC group was not significantly higher than NC group, so endothelial cell dysfunction may not be correlated with metabolic syndrome in the fat rat.Part2The study of relationship between PAI-1、vWF and metabolic disorder in children and adolescent with metabolic syndromeObjective:To study the relationship between children and adolescent metabolic syndrome and endothelial cell dysfunction through detecting the expression of serum PAI-1and vWF in the children and adolescent with metabolic syndrome. Methods: A total of60obese children were enrolled in this trial who were treated in endocrine clinic in general hospital of Tianjin medical university from February2011to February2012consisting30obese patients, including16males and14females, diagnosed as metabolic syndrome30patients, including17males and13females, and age of randomly selected health checkup with normal control children,30cases including15male patients and15females. Height (H), weight (W), waist circumference, blood pressure were measured and body mass index (BMI) was calculated, total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), hsCRP, HbA1c, oral glucose tolerance test (OGTT) were detected. Fasting venous blood samples were collected for the determination of the serum vWF and PAI-1level by Enzyme-linked immunosorbent assay (ELISA). All the datas in the three groups were analyzed statistically and correlation analysis on the level of PAI-1and anthropometric indicators and glucose and lipid metabolism indicators was used. Results:1.The serum activity of vWF and PAI-1in MS group was significantly higher than normal group (P<0.05) the difference was statistically significant,;2. The serum activity of PAI-1in obesty group was significantly higher than normal group (P=0.003),the difference was statistically significant, while the serum activity of vWF was no significantly difference between obesity group and normal group(P=0.556);3. There is a significant positive correlation between PAI-1concentrations and weight、BMI、waist circumference、 TC、TG、LDL、FPG、FINS、SBP、DBP、hsCRP (P<0.05), While a negatively correlated with HDL (P<0.05). There is no significant correlation between PAI-1concentrations and hip circumference,、waist to hip ratio、2hPG、HbA1c (P>0.05).Conclusions:1.Endothelial cell dysfunction is correlated with metabolic syndrome in children and adolescents. vWF and PAI-1can be predicted as clinical indicators of early vascular changes.2. ECD may be correlated with obesity、blood lipid、blood glucose、blood pressure,while TC、TG、FINS may be independent risk factors of ECD.