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Studies On The Relationship Between Modified Low Density Lipoprotein And Atherosclerosis In Type 2 Diabetic Rat And The Protective Effect Of Chinese Herbs

Posted on:2005-03-05Degree:MasterType:Thesis
Country:ChinaCandidate:J B LiFull Text:PDF
GTID:2144360125958351Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Ojective:Macroangiopathy is not only one of the major complications of type 2 diabetes mellitus but also a important factor which threatens human's health.The pathological hallmarks of this complication is atherosclerosis(AS). Modified low density lipoprotein(LDL) which mainly includes oxidized low density lipoprotein (Ox-LDL) and Glycated low density lipoprotein(Gly-LDL) may play the key role during the development of AS. Matrix Metalloproteinase9(MMP-9) could participate in the degradation and reconstruction of ECM in vascular wall and the migration of VSMC,therefore MMP-9 may be one of the important nosogenetic factor of AS. Total panax notoginseng saponins(tPNS) and Astragalus mem- branaceus(Ast) are the common Chinese herbs which could prevent and cure diabetes and its complications.In this study we developed the type 2 diabetic rat model by high-fat diet and a low dose of STZ. This model had the characteristics of hyperlipidemic ,hyperglycemia and insulin resistance,which was similar to that of human type 2 diabetes mellitus.Then the concentration of modified LDL in rats'plasma and the expression of MMP-9 in aorta were examined in order to discuss the pathogenic mechanics of diabetic AS and the functions of two Chinese herbs on AS.Methods:Female SD rats were divided into 2 groups randomly: normal control rats(group A) and test rats.The test rats were fed with high-fat diet (as a percentage of total kcal, the diet consisting of 44% fat,36.1% carbohydrate,19.9% protein) for one month and insulin-resistance was induced .Then after an overnight fast STZ 30mg/kg was injected intraperito neally. Two weeks later,the rats whose blood glucose level was greater than 7.8mmol/L and insulin sensitivity decreased were considered as diabetes.The diabetic rats were randomly divided into following groups:diabetic model rats(group B),diabetic model rats treated with tPNS(group C),and diabetic rats treated with tPNS and Ast (group D).The experiment lasted 18 weeks .After 4 weeks and 6 weeks of the experiment,body weight,blood glucose,insulin and lipids were measured.After 18 weeks of the experiment,blood glucose,serum triglyceride (TG),serum total cholesterol (TC), very low density lipoprotein (VLDL),low density lipoprotein (LDL),high density lipoprotein (HDL),oxidized low density lipoprotein (Ox-LDL) and Glycated low density lipoprotein (Gly-LDL) in plasma were measured. Aorta tissue was stained with HE and observed with microscope. The protein expression of MMP-9 in aorta were measured by immunohistochemical staining. Results were analysed by computer image-analysis system and the IOD of MMP-9 in the rat aorta tissue was counted.Results: 1) 4 weeks after test rats fed by high-fat diet,the rats' weight was heavier than that of group A(P<0.05).Blood glucose,insulin,TG,TC were significantly higher in test rats than that in control rats(all P<0.01).At the same time,insulin sensitive index(ISI) was lower in test groups(P<0.01).2 weeks after STZ injection(6 weeks after experiment), the insulin concentrations of test rats was decreased to the level of control rats.Other features were retained.In test group,the rats' blood glucose had exceeded 7.8mmol/L and the ISI was markedly lower than that in control rats.Up to now ,the diabetic model was accomplished.When the experiment was finished ,blood glucose of group B was much higher than that of group A ( P<0.01),and that of group C and group D was lower than that of group B (all P<0.01). Ox-LDL,Gly-LDL,TG,TC,LDL,VLDL of group B increased significantly than those of group A(all P<0.01).In group C and D,all these indexes decreased obviously compared with group B.HDL in group B was decreased(P<0.01),but increased in group C and D(both P<0.01). Related analysis showed that Ox-LDL had positive correlation with glucose and LDL(r=0.548 P<0.05,r=0.697 P<0.01),negative correlation with HDL(r=-0.685 P<0.01). Gly-LDL had positive correlation with Ox-LDL and glucose (r=0.744 P<0.01,r=0.715 P<0.01).The morphological examination revealed:In group B,the intima thick...
Keywords/Search Tags:oxidized low density lipoprotein, Glycated low density lipoprotein, Matrix Metalloproteinase9, total panax notoginseng saponins, astragalus membranaceus, athero- sclerosis, type 2 diabetic rat
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