Study On The Vascular Remodeling Of Atherosclerosis Rats And Urine Metabonomics Changes

Background: Atherosclerosis(AS)is a common chronic diseases which has sustained and undetectable damage to the whole vascular system,seriously threatens human health.In the past 20 years,with the change of diet structure and the increased pressure,the prevalence of AS in China has been increasing year by year.Vascular remodeling is the outcome of AS,that contains the changes of structure and function.Vascular remodeling is not only the basis of AS itself,but also is the main pathological basis of AS process and some AS-related diseases.Metabolomics is defined as a quantitative measurement of multiparametric metabolic responses of multi-cellular systems to pathophysiological stimuli.RRLC-Q-TOF-MS is particularly well suited for metabolomic analysis since its high sensitivity,high resolving power and high accuracy and is very helpful in identification of metabolites.Objective: 1.To investigate the changes of vascular function and the vascular structure of AS.2.To explore the mechanism of AS based on the applications ofLC-MS.3.Try to identify early biomarkers and potential therapeutic targets for AS.Methods: To establish AS rat models and observe rats' serum TC,TG and LDL.General morphological changes of femoral,carotid and abdominal aorta were observed by HE staining.Isolated artery ring is used to study the changes of vascular function.Application of metabolomics methods by RRLC-QTOF/MS is used to find the biomarker of AS.Results : 1.AS rat models were established,serum TC and LDL were significantly increased.HE staining showed AS group vascular endothelial cells injuried,smooth muscle cells decreased.The contractions of femoral artery and abdominal aorta of AS group induced by NE were increased significantly(p<0.05);the relaxation induced by NTG decreased significantly(p<0.05).2.Seven different metabolites were found between the two groups by RRLC-QTOF/MS,which may be related to the pathogenesis of AS and the process of vascular remodeling.Conclusion: 1.Vascular remodeling has been formed in early AS rats,and its functional changes may be earlier than structural changes.2.RRLC QTOF/MS has shown that glucose metabolism,lipid metabolism,amino acid metabolism,pyrimidine metabolism may play an important function during the AS process.