本文選題：磁共振成像　切入點：超小順磁性氧化鐵顆粒　出處：《廣西醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的1、探討利用超小順磁性氧化鐵(USPIO)偶聯(lián)唾液酸化酶x(s Lex)構建靶向內皮細胞粘附分子-1(ELAM-1)的特異性磁共振成像的分子探針的制備方式,并研究其物理化學特征。2、采取裸鼠構建鼻咽癌移植瘤模型,探究超小順磁性氧化鐵(USPIO)偶聯(lián)唾液酸化酶x(sLex)構成靶向血管內皮細胞粘附分子-1(ELAM-1)的特異性磁共振成像的分子探針(USPIO-PEG-sLex)在鼻咽癌移植瘤的運用價值。方法利用物理沉積方法合成USPIO納米顆粒,通過疏水作用,合成較好水溶性的USPIO-PEG,其表面-COOH充分活化,常溫下與sLex充分孵育,超濾離心和去離子水洗滌,形成磁共振分子探針USPIO-PEG-sLex。采用透射電子顯微鏡(TEM)分析USPIO-PEG-sLex的形態(tài)和粒徑,動態(tài)光散射(DLS)分析偶聯(lián)前與偶聯(lián)后USPIO-PEG-sLex的平均水動力尺寸,粒徑分析儀檢測偶聯(lián)前后USPIO-PEG-s Lex的Zeta電位。將10只鼻咽癌裸鼠移植瘤模型隨機分為實驗組和對照組,分別于尾靜脈注入USPIO-PEG-sLex和USPIO-PEG前后行磁共振T2 mapping成像,比較分析注射造影劑前后移植瘤的T2值變化。MRI掃描完后取移植瘤組織,應用免疫組織化學染色技術分析腫瘤組織新生血管內皮細胞上ELAM-1的表達。結果透射電鏡測定USPIO-PEG平均粒徑為10±2.6nm,分散性較好,大小適宜;動態(tài)光散射測定偶聯(lián)前后其平均水動力尺寸分別為(34.06±9.95)nm,(53.35±16.99)nm;偶聯(lián)前的PEG化磁性納米顆粒的Zeta電位為(11.6±3.96)mV,偶聯(lián)后為(-12.6±5.33)mV。USPIO-PEG-s Lex具有良好表征。對照組和實驗組的鼻咽癌移植瘤的平掃T2值差異沒有統(tǒng)計學意義(PO.05),增強掃描后兩組的T2值下降,兩組的T2值差異有統(tǒng)計學意義(PO.05);實驗組的強化率更低,兩組的強化率差異有統(tǒng)計學意義(P0.05)。實驗組中瘤體與肌肉的強化率差異有統(tǒng)計學意義(PO.05)。免疫組化結果顯示E-選擇素蛋白在血管內皮細胞胞漿或胞膜呈棕黃色表達。HE染色結果顯示胞核為深藍色且具有顯著異型性,胞漿及纖維組織為深淺不一的紅色。結論化學交聯(lián)法可成功制備磁共振分子探針USPIO-PEG-sLex,該分子探針的表征良好,有望用于體內、外實驗特異性地結合ELAM-1。USPIO-PEG-s Lex納米磁性顆粒有望作為鼻咽癌ELAM-1表達的靶向造影劑,在非創(chuàng)傷動態(tài)監(jiān)測ELAM-1的表達方面具有良好的潛在應用前景。
[Abstract]:Objective 1 to investigate the preparation of a molecular probe for specific magnetic resonance imaging targeting endothelial cell adhesion molecule-1 (ELAM-1) using ultra-small paramagnetic ferric oxide USPIO-coupled salivary acidifier xs Lexus. The physicochemical characteristics of nasopharyngeal carcinoma (NPC) were studied in nude mice, and the model of transplanted nasopharyngeal carcinoma (NPC) was established in nude mice. To explore the application value of USPIO-PEG-sLexus, a molecular probe for magnetic resonance imaging targeting vascular endothelial cell adhesion molecule-1 (ELAM-1), coupled with the salivary acidifier xansLexus, in the treatment of nasopharyngeal carcinoma (NPC) transplanted tumors. Methods physical deposition was used to investigate the application of USPIO-PEG-sLexs in nasopharyngeal carcinoma (NPC) xenografts. Methods USPIO nanoparticles were synthesized. A better water-soluble USPIO-PEG was synthesized by hydrophobic interaction. The surface of USPIO-PEG was fully activated, fully incubated with sLex at room temperature, ultrafiltration centrifugation and deionized water washing to form magnetic resonance molecular probe USPIO-PEG-sLex.Tem was used to analyze the morphology and particle size of USPIO-PEG-sLex. Dynamic light scattering (DLS) was used to analyze the mean hydrodynamic size of USPIO-PEG-sLex before and after coupling. The Zeta potential of USPIO-PEG-sLex before and after coupling was measured by particle size analyzer. Ten nude mice with nasopharyngeal carcinoma were randomly divided into experimental group and control group. The T 2 mapping imaging was performed before and after the injection of USPIO-PEG-sLex and USPIO-PEG into the caudal vein. The T 2 value of the transplanted tumor before and after the injection of contrast media was compared and analyzed. The expression of ELAM-1 on tumor neovascularization endothelial cells was analyzed by immunohistochemical staining. Results the average diameter of USPIO-PEG was 10 鹵2.6 nm by transmission electron microscopy. The mean hydrodynamic size before and after coupling was 34.06 鹵9.95 nmnmand the Zeta potential of the PEG magnetic nanoparticles before coupling was 11.6 鹵3.96mV, and that after coupling was -12.6 鹵5.33mV.USPIO-PEG-s Lex. The Zeta potential of the nasopharyngeal carcinoma transplanted tumor in the control group and the experimental group was better than that in the control group and the experimental group. There was no significant difference in T _ 2 value between the two groups, but the T _ 2 value of the two groups decreased after enhanced scan. The T2 value of the two groups was significantly different from that of the control group, and the enhancement rate of the experimental group was lower than that of the control group. There was significant difference in enhancement rate between the two groups (P 0.05). There was a significant difference between the enhancement rate of tumor and muscle in the experimental group (P < 0.05). The immunohistochemical results showed that the expression of Eselectin protein in the cytoplasm or membrane of vascular endothelial cells was brownish yellow. The staining results showed that the nucleus was dark blue and had significant heterogeneity. Conclusion the magnetic resonance molecular probe USPIO-PEG-sLexus can be successfully prepared by chemical crosslinking. ELAM-1.USPIO-PEG-s Lex nanoparticles can be used as a target contrast agent for ELAM-1 expression in nasopharyngeal carcinoma and have a good potential application in non-invasive dynamic monitoring of ELAM-1 expression.
【學位授予單位】：廣西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R445.2;R739.63

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