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  本文關(guān)鍵詞： 口服免疫耐受 動脈粥樣硬化 HsP6O ApoE~(-/-)小鼠 模型　出處：《吉林大學》2011年碩士論文　論文類型：學位論文

【摘要】：動脈粥樣硬化(atherosclerosis, AS)所致的心、腦血管疾病已嚴重危害人類生命健康。隨著社會的發(fā)展和各方面競爭壓力的增加,動脈粥樣硬化對人類健康的影響與日俱增。因此,建立理想的口服免疫耐受模型在抗動脈粥樣硬化疾病的研究中有重要意義。 本研究旨在通過構(gòu)建動脈粥樣硬化模型,檢測口服小劑量熱休克蛋白60(HSP60)干預對動脈粥樣硬化模型的建立的影響。進一步分析口服HSP60與動脈粥樣硬化的關(guān)系,為進一步研究口服免疫耐受在抗動脈粥樣硬化的作用及機制及治療心血管疾病提供新的靶點及理論依據(jù)。 目的：口服HSP60誘導免疫耐受對動脈粥樣硬化的影響及相關(guān)因素的評價。 方法：健康雄性8周齡ApoE-/-小鼠,16只,隨機分為高脂對照組、HSP60組。小鼠分別給予單純蒸餾水和重組小鼠HSP60+生理鹽水+長鏈甘油三酯隔天灌胃,共4次,末次灌胃7d后腹腔注射等劑量的HSP60,高脂飼養(yǎng)10周后進行實驗。實驗過程中每7-10天測定小鼠體重,實驗結(jié)束后收集主動脈弓段組織制作病理組織切片,HE染色以觀察組織學的變化及比較斑塊面積大小。 結(jié)果：(1)高脂飲食4周后高脂組小鼠出現(xiàn)嗜睡,飲食、飲水增多,一般活動減少。HSP60組小鼠行為表現(xiàn)及各種活動均正常。(2)高脂飲食4周后,高脂組與HSP60組體重增長比較具有統(tǒng)計學差異(P＜0.01),HSP60組體重增長慢于高脂組。(3)主動脈段HE染色：高脂組主動脈內(nèi)斑塊形成明顯,主動脈管腔形成狹窄。HSP60組管腔內(nèi)膜僅略不光滑,未見明顯狹窄形成。(4)計算動脈粥樣硬化斑塊面積：病理圖像分析儀計算斑塊面積各組ApoE-／-小鼠主動脈粥樣斑塊面積,HSP60口服組主動脈粥樣斑塊面積(無斑塊形成)明顯小于高脂組斑塊面積[(2202.89±524.25)μm2](P＜0.01)。 結(jié)論：(1)、本實驗通過高脂喂養(yǎng)ApoE-/-小鼠建立合理的動脈粥樣硬化模型。(2)、應(yīng)用HSP60具有明顯的抗動脈粥樣硬化作用。(3)、本實驗所建立的動物模型可以用于口服免疫耐受抗動脈粥樣硬化的研究,其為進一步闡明口服免疫耐受通過上調(diào)CD4+ CD25+調(diào)節(jié)性T細胞進而預防動脈粥樣硬化及冠心病的發(fā)病與進展方面奠定了實驗基礎(chǔ)。
[Abstract]:Atherosclerosis caused by atherosclerotic disease (ASA) has been seriously harmful to human life and health. With the development of society and the increase of competition pressure in all aspects. The influence of atherosclerosis on human health is increasing. Therefore, it is important to establish an ideal oral immune tolerance model in the study of anti-atherosclerotic diseases. The purpose of this study was to construct an atherosclerosis model. To detect the effect of oral heat shock protein 60 (HSP60) on the establishment of atherosclerosis model, and to further analyze the relationship between oral HSP60 and atherosclerosis. To further study the role and mechanism of oral immune tolerance in anti-atherosclerosis and to provide a new target and theoretical basis for the treatment of cardiovascular disease. Objective: to evaluate the effect of oral HSP60 induced immune tolerance on atherosclerosis. Methods: sixteen healthy male 8-week-old ApoE-r-mice were randomly divided into hyperlipidemic control group. HSP60 group. Mice were given intraperitoneal injection of HSP60 of the same dose respectively with distilled water and recombinant HSP60 saline with long chain triglyceride for 4 times every other day. The body weight of mice was measured every 7-10 days after high-fat feeding for 10 weeks. After the experiment, the aortic arch tissues were collected to make pathological sections. HE staining was used to observe histological changes and to compare the size of plaques. Results (1) after 4 weeks of high-fat diet, mice in high-fat group appeared drowsiness, diet and drinking water increased. The general activity decreased. HSP60 group showed normal behavior and all kinds of activities. 2) after 4 weeks of high fat diet. There was significant difference in weight gain between high fat group and HSP60 group (P < 0.01). The weight gain of HSP60 group was slower than that of hyperlipidemia group. No significant stenoses formation was observed.) Atherosclerotic plaque area was calculated by pathological image analyzer. ApoE-r-a-mouse aortic atherosclerotic plaque area was calculated by pathological image analyzer. Atheromatous plaque area (no plaque formation) in HSP60 group was significantly smaller than that in high fat group. [2202.89 鹵524.25 渭 m ~ 2] P < 0.01. Conclusion in this experiment, we established a reasonable atherosclerosis model by high-fat feeding ApoE-r-mice. HSP60 has obvious anti-atherosclerotic effect. The animal model established in this study can be used to study the anti-atherosclerosis of oral immune tolerance. It provides an experimental basis for further elucidation of oral immune tolerance in preventing atherosclerosis and coronary heart disease by upregulating CD4 CD25 regulatory T cells.
【學位授予單位】：吉林大學
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R-332;R543.5

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本文編號：1451842