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To Study The Effects Of AngⅡ Up Regulating Th17/IL-17Expression On Atherosclerosis

Posted on:2014-11-05Degree:MasterType:Thesis
Country:ChinaCandidate:J H XieFull Text:PDF
GTID:2254330425458336Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objectives:This thesis aims to employ benazepril to inhibit the growth of AngⅡ to observethe influence of AngⅡ on atherosclerosis and to explore the role of Th17/IL-17onAngⅡ regulating the formation of atherosclerosis.Methods:(1)The vascular of rabbits are injuried by the balloon of catheter and the rabbitare fed on high lipid to establish the rabbit model of atherosclerosis with the methodof Chekanov’s and Yu Lina’s introduction. The rabbits are fed for12weeks,Theultrasonic is employed to prove formation of the left common carotid arteryplaque as a mark of success of the rabbit model of atherosclerosis.(2)grouping, breeding, and drug delivery of experiment:22male New Zealandwhite rabbits are divided into two groups,6in the normal control group and16inmodel group in a randomized complete block design. Model rabbits are divided intohigh fat group and benazepril group in random.①normal control group: eachexperimental rabbit is fed with100g ordinary forage(50g in the morning and50g atnight)every day.②high fat group: each experimental rabbit is fed with high100gfat forage (50g in the morning and50g at night)and is filled with physiologicalsaline in its stomach2mg.kg-1.d-1every day.③benazepril group: eachexperimental rabbit is fed with100g high fat forage(50g in the morning and50g atnight)and is filled with benazepril in its stomach2mg.kg-1.d-1.(3)The rabbits are fed for12weeks, artery atheromatous plaque and lipid sizeare observed with naked eyes and HE staining; The serum lipid levels (totaltriglycerides, total cholesterol, high density lipoprotein cholesterol, low densitylipoprotein, very low density lipoprotein) are tested with7600full automaticbiochemical analyzer; The plasma AngⅡ levels are tested with ria kit; plasma IL-17levels are tested with ELISA kit; The ROR-γt mRNA levels of spleen tissue are testedwith RT–PCR; The plasma hs-CRP levels are tested with ELISA kit. Results:(1)4rabbits died in the experimental process and18rabbits survive. Animalsurvival rate is81.81%.(2)The rabbits are fed for12weeks, with the naked eyes view, uneven surfaceand grease hyperplastic material is not seem in rabbit aorta intima of normal controlgroup. grease material hyperplastic,uneven surface is seem in rabbit aorta intima ofhigh fat group and they projecte from the lumen. The lesions in rabbit aorta intima ofbenazepril group are similar to those of high fat group, but lesions of the rabbit aortaintima are more mild than those of benazepril group. similar results of the rabbit aortaare found on HE staining slice. uneven surface, foam cells and grease materialhyperplastic are not seen in the rabbit aorta intima of normal control group. obvioushyperplasia, a lot of foam cells, Collagen, grease material hyperplastic, the plaque ofcalcification and lipid are seen in the rabbit aorta intima of high fat group.hyperplasia and foam cells, Collagen, the plaque of calcification and lipid are seen inthe rabbit aorta intima of high fat group, but lesions of benazepril group are moremild than those of benazepril group.(3)The rabbits are fed for12weeks.The blood lipids levels(TC, TG, HDL-C,LDL-C, VLDL-C) of normal control group respectively are1.29±0.71mmol/L,1.16±0.68mmol/L,0.51±0.15mmol/L,0.65±0.50mmol/L and0.67±0.16mmol/L;Those of high fat group are29.1±1.86mmol/L,5.89±5.91mmol/L,1.19±2.66mmol/L,19.0±1.03mmol/L and8.02±2.78mmol/L; Those of benazepril group are28.7±1.50mmol/L,6.64±5.69mmol/L,2.42±2.45mmol/L,16.7±4.37mmol/L and6.93±2.91mmol/L. F values of TC, LDL-C and VLDL-C respectively are737.29,88.95and20.07and the differences respectively are statistically significant by singlefactor analysis of variance. F values of TG, HDL-C respectively are2.36,1.135andthe differences are not statistically significant. TC, LDL-C and VLDL-C levels ofhigh fat group and the benazepril group are compared to those of normal controlgroup and the differences respectively are statistically significant. TC, LDL-C,VLDL-C levels of the benazepril group respectively are compared to those of high fatgroup and the differences are not statistically significant by SNK-q analysis.(4)The rabbits are fed for12weeks, plasma AngⅡ level of normal controlgroup is1238.32±125.60pg/mL. That of high fat group is1554.38±32.23pg/mL. That of benazepril group is1419.76±32.78pg/mL. F values is25.32and the difference isstatistically significant by single factor analysis of variance and SNK-q analysis.(5)The rabbits are fed for12weeks, plasma IL-17level of normal controlgroup is96.79±28.29pg/mL.That of high fat group is221.50±36.54pg/mL. That ofbenazepril group is157.05±41.68pg/mL. F values is18.08and the difference isstatistically significant by single factor analysis of variance and SNK-q analysis.(6)The rabbits are fed for12weeks, ROR-γt mRNA levels of the spleen tissueof rabbits is0.4、0.96、0.76by rabbits’ROR-γt/β-actin ratio and the difference isstatistically significant by single factor analysis of variance and SNK-q analysis.(7)The rabbits are fed for12weeks, Between plasma AngⅡ levels and IL-17levels is positively related. R is0.79and linear regression equation isY0.33X301.1and the equation is statistically significant.(8)The rabbits are fed for12weeks, Between plasma AngⅡ levels andRORγt/β-actin ratio is positively related. R is0.67and linear regression equation isY0.001X1.38and the equation is statistically significant.(9)The rabbits are fed for12weeks, plasma hs-CRP level of normal controlgroup is0.96±0.42mg/L. That of high fat group is21.91±5.02mg/L. That ofbenazepril group is13.23±4.02mg/L and the difference is statistically significant bysingle factor analysis of variance and SNK-q analysis.(10)The rabbits are fed for12weeks, Between plasma IL-17levels andhs-CRP levels is positively related. R is0.74and linear regression equation isY0.11X5.75and the equation is statistically significant.Conclusions:(1)The methods of using the balloon of catheter to injury vascular and feedinghigh lipid can successfully establish the rabbit model of atherosclerosis.(2)AngⅡ bring about the formation of atherosclerosis.Amechanism of them isthat AngⅡ increases expression of Th17/IL-17and it may cause and aggravate theinflammation of body in occurrence and development of atherosclerosis.(3)Benazepril inhibit the formation of atherosclerosis by reducing thegeneration of AngⅡ and inflammatory factors.
Keywords/Search Tags:AngⅡ, atherosclerosis, Th17/IL-17, hs-CRP
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