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The Mechanism Of Kudzu Vine Root On Reducing Endothelial Cell Damagement By Methylglyoxal,based On Non-enzymatic Glycosylation Reaction

Posted on:2018-08-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y YuanFull Text:PDF
GTID:2334330542471308Subject:Clinical Pharmacy
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ResearchbackgroundDiabetes is a chronic systemic metabolic diseases,withhyperglycemia.The mechanism of diabetes may be due to insulin secretion deficiency or damage to its biological function,or both.Its development is generally associated with a variety of complications,such as cardiovascular,renalocular fundus and nervous system disease,but diabetic angiopathy were the main causes of death in diabetes patient.At home and abroad in recent years a large number of studies have shown that the non-enzymatic glycosylation is one of the main pathogenesis of diabetic angiopahty,it is combined by the protein of amino group and aldehyde group of sugar,unstable schiff alkali formed first,irreversible terminal products AGEs come into being by molecular rearrangement,this irreversible AGEs accumulate in vivo which damage to the structure of crosslinking protein,promoting oxidative stress reaction in organism and causing the development of diabetic vascular complications.Research shows that the oxidative stress caused by combination of AGEs and the receptors can lead to the changes in renal structure and functionActive dicarbonyl compounds were precursor of AGEs,which belongs to the high reactivity glycosylation factor,studies have shown that a variety of traditional Chinese medicine active ingredients can inhibit production of AGEs by preventing saccharification or remove oxide active dicarbonyl compounds etc.Kudzu vine root is the dry root of Puerarialobata(Willd.)Ohwi,perennial leguminous deciduous vines,is used as activationg blood circulation medicine for treatment of hypertension?diabetes?angina and retinopathy and so on.puerarin,the main active ingredient from Kudzu vine root,which has strong antopxidation,can decrease blood glucose,improve microcirculation,protect endothelial cells.In this study,Establishment of model of diabetes in C57BL/6 mice induced by high-glucose-high-fat diet and streptozotocin(40 mg·kg-1),value of AGEs were assessed by lead fluorophotometry,we investigated the rules of AGEs inhibitory action of puerarin.,for finding the effect and the mechanism of Kudzu vine roo for reducing the diabetic vascular complications caused by endothelial cell damagement.ObjectiveTo provide scientific bases for the further creation of new Chinese medicine for prevention and treatment of diabetic vascular complications,this study is based on non-enzymatic glycosylation reaction,with simulation reaction conditions,detecting ingredients change after reaction between Kudzu vineextraction and methylglyoxal,to screen out the active constituent in kudzu root which can catch carbonyl compound and investigate the mechanism of inhibition for AGEs of kudzu root.MethodsEstablishment of model of diabetes in C57BL/6 mice induced by high-glucose-high-fat diet and streptozotocin(40 mg·kg-1),then divide model into model set?Aminoguanidine group(100 mg·kg-1)?low-dose puerarin group(50 mg· kg-1)?middle-dose puerarin group(100 mg·kg-1)?high-dose puerarin group(200 mg·kg-1),and control group,next detect the fasting blood glucose(FBG)?oral glucose test(OGTT)?glycosylated serum protein(GSP)?Serum creatinine(Scr)and serum AGEs.besides,the incubation contain puerarin of different concentration(0.5?1.0?2.0 ?mol·L-1)?Methylglyoxal and Bovine serum albumin last for 44 hours,non-enzymatic glycosylation reaction model in vitro were established,fluorescence value of AGEs were assessed by lead fluorophotometry,finally investigate the rules of AGEs inhibitory action of puerarin.Resultspuerarin can significantly reduce the fasting blood glucose of diabetic mice,improve oral glucose tolerance,debase the GSP and the change in renal structure and function,control the serum AGEs.in addition,puerarin can inhibit the AGEs in non-enzymatic glycosylation reaction system in vitro dose-dependently.Conclusionpuerarin had remarkable effects on diabetic vascular complications,and controlling the creating of AGEs may be the potential mechanism.
Keywords/Search Tags:puerarin, non-enzymatic glycosylation, advanced glycosylation end products, diabetes mellitus
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