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老年恒河猴頸動脈粥樣硬化性狹窄模型的建立

發(fā)布時間:2018-06-28 15:58

  本文選題:頸動脈狹窄 + 動物模型��; 參考:《廣西醫(yī)科大學(xué)》2013年碩士論文


【摘要】:目的本實(shí)驗(yàn)將通過使用球囊損傷聯(lián)合高脂飼料喂養(yǎng)的方法,初步建立能夠模擬人類由于動脈粥樣硬化引起的頸動脈狹窄的老年恒河猴模型。為進(jìn)一步研究人類頸動脈狹窄在缺血性腦血管病(ischemic cerebrovascular disease ICVD)的發(fā)生以及發(fā)展中的作用提供實(shí)驗(yàn)依據(jù)。 方法4只體重相近的雄性老齡(15歲)恒河猴,隨機(jī)分配為實(shí)驗(yàn)組和對照組,每組2只。采取股動脈穿刺的方法,使用球囊擴(kuò)張損傷實(shí)驗(yàn)組動物左側(cè)頸動脈(left carotid artery L-CA)中段,聯(lián)合高脂飼料喂養(yǎng)14周,對照組僅使用基礎(chǔ)飼料喂養(yǎng)。在喂養(yǎng)過程中,每2周對恒河猴進(jìn)行神經(jīng)系統(tǒng)功能的評分、稱量體重及血脂水平的檢測,每4周進(jìn)行頸部血管的超聲檢查。14周后,再次進(jìn)行全腦血管造影術(shù),評價(jià)血管狹窄形成的情況,通過北美癥狀性頸動脈內(nèi)膜剝脫術(shù)試驗(yàn)(american symptomatic carotid endarterectomy trial NASECT)法計(jì)算血管的狹窄率。 結(jié)果 1.體重的變化:在喂養(yǎng)期間,實(shí)驗(yàn)組動物的體重隨測量時間而變化,并且呈現(xiàn)出逐漸增長的趨勢,與對照組的差異有統(tǒng)計(jì)學(xué)意義(P0.05); 2.血脂水平的變化:在喂養(yǎng)期間,實(shí)驗(yàn)組的血清總膽固醇(serum total cholesterol TC),甘油三酯(triglyceride TG),載脂蛋白B (apolipoprotein B ApoB)及低密度脂蛋白膽固醇(low density lipoprotein cholesterol LDL-C)的含量隨喂養(yǎng)時間而變化,并且呈顯著的增高趨勢,與對照組差異有統(tǒng)計(jì)學(xué)意義(P0.05);而實(shí)驗(yàn)組的載脂蛋白A1(apolipoprotein A1ApoA1)和高密度脂蛋白膽固醇(high density lipoprotein cholesterol HDL-C)與對照組相比則沒有明顯的增高趨勢(P0.05); 3.神經(jīng)系統(tǒng)功能評分的變化:14周的喂養(yǎng)時間內(nèi),所有實(shí)驗(yàn)動物神經(jīng)系統(tǒng)功能評分始終為0分,未出現(xiàn)神經(jīng)系統(tǒng)功能缺失。 4.頸動脈超聲多普勒的結(jié)果:通過超聲檢查顯示實(shí)驗(yàn)組損傷側(cè)頸動脈中部出現(xiàn)動脈粥樣硬化性改變:血流速度較前增快,收縮期血流速度(velocity during systole Vs)和舒張期血流速度(velocity during diastole Vd):猴1分別為135.6cm/s和24.8cm/s,猴2分別為141.6cm/s和36.4cm/s;管腔分別為1.8mm和1.6mm,較前減��;同時,還可以觀察到內(nèi)膜增厚,內(nèi)-中膜厚度(intima-media thickness of artery IMT)為1.1mm和1.2mm。而實(shí)驗(yàn)組非損傷側(cè)和對照組則接近正常。 5.復(fù)測全腦血管造影的結(jié)果:喂養(yǎng)結(jié)束后腦血管造影顯示實(shí)驗(yàn)組L-CA直徑分別為1.25mm和1.37mm, R-CA分別為2.38mm和2.41mm,通過計(jì)算左側(cè)狹窄率分別為46.1%及45.8%,而對照組的左側(cè)直徑分別為2.33mm和2.35mm,右側(cè)為2.42mm和2.39mm,沒有狹窄形成。 結(jié)論通過使用球囊擴(kuò)張聯(lián)合高脂飼料喂養(yǎng)的方法,可以初步地建立伴有體重和血脂水平增高的頸動脈粥樣硬化性狹窄的恒河猴模型,超聲及DSA檢測可見頸動脈內(nèi)有斑塊形成、管腔狹窄。該模型能較好的模擬人類在高脂血癥環(huán)境下所發(fā)生的頸動脈粥樣硬化斑塊的形成,為研究人類頸動脈狹窄在導(dǎo)致ICVD的發(fā)生以及疾病的進(jìn)展過程中的作用提供了寶貴的實(shí)驗(yàn)依據(jù)。
[Abstract]:Objective the aim of this study is to establish an elderly Ganges RIver monkey model which can simulate human carotid stenosis caused by atherosclerosis by using balloon injury combined with high fat feed. To further study the occurrence and development of human carotid stenosis (ischemic cerebrovascular disease ICVD) in human carotid artery stenosis. The role of the exhibition provides experimental basis.
Methods 4 Ganges RIver monkeys, aged 15 years of age (15 years old), were randomly assigned to the experimental group and the control group, with 2 rats in each group. The left carotid artery (left carotid artery L-CA) in the balloon dilatation injury experimental group was fed with the middle part of the left carotid artery (artery L-CA), and the high fat diet was fed for 14 weeks, and the control group was fed with only basic feed. In the course, the neurological function of Ganges RIver monkeys was scored every 2 weeks, weighing the body weight and blood lipid level. After 4 weeks of cervical vascular ultrasound examination.14 weeks, the whole brain angiography was carried out again to evaluate the formation of vascular stenosis and through the North American symptomatic carotid artery intima exfoliation test (American Symptomatic Carotid end). Arterectomy trial NASECT method was used to calculate the stenosis rate of blood vessels.
Result
1. changes in weight: during the feeding period, the weight of the animals in the experimental group changed with the measured time, and showed a trend of gradual growth. There was a significant difference between the control group and the control group (P0.05).
2. changes in blood lipid level: during the feeding period, the serum total cholesterol (serum total cholesterol TC), triglyceride (triglyceride TG), apolipoprotein B (apolipoprotein B ApoB) and low density lipoprotein cholesterol (low density) were changed with feeding time, and increased significantly. There was a significant difference between the control group and the control group (P0.05), while the apolipoprotein A1 (apolipoprotein A1ApoA1) and the high density lipoprotein cholesterol (high density lipoprotein cholesterol HDL-C) in the experimental group were not significantly higher than those of the control group (P0.05).
3. changes in the function score of the nervous system: during the feeding time of 14 weeks, the neurological function score of all the experimental animals was always 0, and no nervous system dysfunction was found.
4. results of carotid ultrasound Doppler: ultrasound examination showed atherosclerotic changes in the central carotid artery in the experimental group: the blood flow velocity was faster than before, the systolic blood velocity (velocity during systole Vs) and the diastolic blood flow velocity (velocity during diastole Vd): monkey 1 were 135.6cm/s and 24.8cm/s, monkey 2, respectively. 141.6cm/s and 36.4cm/s, respectively, the lumen were 1.8mm and 1.6mm, respectively. At the same time, the intima thickening was observed, the thickness of the inner middle membrane (intima-media thickness of artery IMT) was 1.1mm and 1.2mm., while the non injury side and the control group were close to normal in the experimental group.
5. results of total cerebral angiography: after feeding, cerebral angiography showed that the diameter of L-CA in the experimental group was 1.25mm and 1.37mm, R-CA was 2.38mm and 2.41mm respectively. The left stenosis rate was 46.1% and 45.8%, respectively, while the left diameter of the control group was 2.33mm and 2.35mm, and the right was 2.42mm and 2.39mm, and no stenosis was formed.
Conclusion by using balloon dilatation combined with high fat feed, the Ganges RIver monkey model with carotid atherosclerotic stenosis with higher body weight and high blood lipid level can be initially established. Plaque formation and stenosis in the carotid artery can be detected by ultrasound and DSA. This model can better simulate human hair in hyperlipidemia environment. The formation of atherosclerotic carotid atherosclerotic plaques provides valuable experimental evidence for the study of the role of human carotid artery stenosis in the development of ICVD and the progress of the disease.
【學(xué)位授予單位】:廣西醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2013
【分類號】:R-332;R543.4

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