本文選題：動脈粥樣硬化 + 載脂蛋白E類　； 參考：《南京醫(yī)科大學》2017年碩士論文

【摘要】：目的1.檢測Tenascin-C在ApoE-/-小鼠動脈粥樣硬化斑塊形成過程中,不同時期(4、8、16、24、32w)表達的動態(tài)變化,探討其表達特性。2.探討MR靶向探針anti-Tenascin-C-USPIO在動脈粥樣硬化斑塊中的特異性成像,為臨床動脈粥樣硬化分子成像的應(yīng)用提供實驗依據(jù)。材料和方法1.取ApoE基因敲除(ApoE-/-)小鼠50只,高脂飼料喂養(yǎng),建立小鼠動脈粥樣硬化(AS)模型,C57BL/6小鼠50只為同源對照組,普通飲食喂養(yǎng)。分別于喂養(yǎng)第4、8、16、24、32周(w)時處死小鼠,檢測血脂,顯微鏡觀察斑塊病理改變并進行定量分析,免疫組織化學方法檢測動脈粥樣硬化斑塊內(nèi)Tenascin-C的表達。2.20只ApoE-/-小鼠予高脂飲食喂養(yǎng)建立動脈粥樣硬化模型,將其分為靶向探針組10只,對照組10只,分別喂養(yǎng)至16、24w,探針組注射anti-Tenascin-C-USPIO,對照組注射單純USPIO(n=5/組/周),于注射24h后進行7.0T MR成像,檢測斑塊信號改變。成像后立刻取主動脈標本進行Tenascin-C免疫組化染色,并行普魯士藍染色,觀察斑塊內(nèi)鐵沉積。結(jié)果1.模型組總膽固醇(TC)、低密度脂蛋白(LDL)水平均高于對照組(P均0.05)。隨著造模時間的進展,模型組斑塊面積及斑塊面積/管腔面積比值不斷增加,各時期比較均有統(tǒng)計學意義(P0.05)。模型組斑塊內(nèi)Tenascin-C表達量隨著AS進展而升高,AS 32w小鼠斑塊內(nèi)部Tenascin-C表達升高最顯著,高于8、16、24w 小鼠(0.49±0.07vs0.04±0.02,0.12±0.03,0.21±0.04,P0.05)。2.靶向探針組的斑塊信號改變率較對照組明顯降低(16w:-15.65 ±0.78%vs.-3.43 ± 2.57%;24w:-26.38 ± 1.54%vs.-11.12 ± 1.60%,P0.05)。并且在靶向探針組中,24w時斑塊的信號改變率較16w亦明顯降低(P0.05)。免疫組化染色顯示探針組Tenascin-C隨著斑塊進展表達升高,與MR圖像斑塊信號改變程度相一致。普魯士藍染色顯示探針組斑塊內(nèi)較多藍染顆粒,而對照組則極少。結(jié)論1.Tenascin-C的表達量隨著斑塊進展不斷增加,主要表達于脂核周圍及破裂的纖維帽中,Tenascin-C的表達水平變化可能與動脈粥樣硬化進展及斑塊不穩(wěn)定性有關(guān)。2.7.0TMR可以對ApoE-/-小鼠動脈粥樣硬化斑塊模型進行活體評估。anti-Tenascin-C-USPIO探針可實現(xiàn)小鼠動脈粥樣硬化斑塊的靶向MR體內(nèi)成像,用于監(jiān)測斑塊的進展,為動脈粥樣硬化分子成像的進一步開展奠定了基礎(chǔ)。
[Abstract]:Objective 1. To detect the dynamic changes of Tenascin-C expression in ApoE-r-mouse atherosclerotic plaques (ApoE-R-mice) at different stages (4 ~ 816 ~ 24 ~ 32w) and to explore its expression characteristics. 2. To investigate the specific imaging of Mr targeted probe anti-Tenascin-C-USPIO in atherosclerotic plaques, and to provide experimental evidence for the application of molecular imaging in clinical atherosclerosis. Materials and methods 1. Fifty ApoE knockout mice were fed with high fat diet and 50 C57BL / 6 mice were fed with common diet. The mice were killed after feeding for (w) at the 4th week of 816 and 2432 weeks, the blood lipids were detected, the pathological changes of plaques were observed by microscope and quantitative analysis was made. Immunohistochemical method was used to detect the expression of Tenascin-C in atherosclerotic plaques. 2.20 ApoE-r-mices were fed with high-fat diet to establish atherosclerosis model. They were divided into target probe group (n = 10) and control group (n = 10). The probe group was injected with anti-Tenascin-C-USPIOand the control group was injected with simple USPIO (5 / week). After 24 hours of injection, 7.0T Mr imaging was performed to detect the changes of plaque signal. Immediately after imaging, the aortic specimens were stained with Tenascin-C immunohistochemical staining and Prussian blue staining to observe the iron deposition in the plaques. Result 1. The levels of total cholesterol (TC) and low density lipoprotein (LDL) in the model group were higher than those in the control group (P 0.05). With the progress of modeling time the plaque area and plaque area / lumen area ratio in the model group increased continuously and there were significant differences in each period (P0.05). The expression of Tenascin-C in atherosclerotic plaques in the model group was significantly increased with the progression of atherosclerosis. The expression of Tenascin-C in the atherosclerotic plaques was significantly higher than that in the mice at 816 ~ 24w (0.49 鹵0.07vs0.04 鹵0.02 鹵0.12 鹵0.03 鹵0.21 鹵0.04p0.05) .2.The expression of Tenascin-C in atherosclerotic plaques was significantly higher than that in the control group. The change rate of plaque signal in the target probe group was significantly lower than that in the control group (16w:-15.65 鹵0.78%vs.-3.43 鹵2.57B, 24w: -26.38 鹵1.54%vs.-11.12 鹵1.60,P0.05). In the target probe group, the signal change rate of plaque at 24 weeks was significantly lower than that of 16 weeks (P0.05). Immunohistochemical staining showed that the expression of Tenascin-C in the probe group increased with the progression of plaque, which was consistent with the change of plaque signal in Mr images. Prussian blue staining showed that there were more blue-stained granules in the probe group than in the control group. Conclusions 1. The expression of Tenascin-C increased with the progression of plaque. The expression level of Tenascin-C mainly expressed around the adipoid nucleus and in the ruptured fibrous cap may be related to the progression of atherosclerosis and plaque instability. 2.7.0 TMR can be used to evaluate the ApoE-r-mouse model of atherosclerotic plaque in vivo. Anti-Tenascin-C-USPIO probe. In vivo Mr imaging of atherosclerotic plaques in mice can be achieved by acupuncture. It can be used to monitor the progress of plaque and lay the foundation for further development of atherosclerotic molecular imaging.
【學位授予單位】：南京醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R543.5;R445.2

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