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三種磁性納米粒子作為MRI對(duì)比劑的探索研究

發(fā)布時(shí)間:2018-06-22 15:49

  本文選題:SPIOs + 油酸鈉 ; 參考:《重慶醫(yī)科大學(xué)》2014年碩士論文


【摘要】:目的制備油酸鈉(sodium oleate)、殼聚糖(chitosan)和葡聚糖(dextran)修飾的超順磁性四氧化三鐵納米粒(SPIOs),并對(duì)其進(jìn)行表征,研究其對(duì)大鼠的急性毒性效應(yīng),評(píng)估其作為磁共振對(duì)比劑的成像效果,為進(jìn)一步優(yōu)化磁共振對(duì)比劑配方提供實(shí)驗(yàn)基礎(chǔ)。 方法(1)化學(xué)共沉淀法合成油酸鈉、殼聚糖和葡聚糖三種不同表面修飾的SPIOs,通過激光衍射分析儀,透射電鏡及振動(dòng)磁強(qiáng)計(jì)對(duì)其進(jìn)行形貌結(jié)構(gòu)觀察、粒徑分布和磁性性能表征。(2)選用SD大鼠72只,隨機(jī)分為生理鹽水對(duì)照組、油酸鈉-SPIOs組、殼聚糖-SPIOs組和葡聚糖-SPIOs組,10%水合氯醛腹腔麻醉后尾靜脈給藥,劑量100μmol/kg,對(duì)大鼠的一般情況進(jìn)行觀察記錄,于給藥后第1天、第3天和第14天隨機(jī)處死每組中6只大鼠,腹腔靜脈取血檢測(cè)肝腎功血生化指標(biāo)。(3)選用SD大鼠32只隨機(jī)分為生理鹽水對(duì)照組、油酸鈉-SPIOs組、殼聚糖-SPIOs組和葡聚糖-SPIOs組,10%水合氯醛腹腔麻醉后尾靜脈給藥,,分別于給藥后10min、30min、60min、3h、6h在GE1.5T磁共振掃描儀上進(jìn)行掃描,采用3英寸線圈,SE T2map、FRFSE T2WI序列掃描,對(duì)應(yīng)用不同修飾材料SPIOs時(shí)的弛豫時(shí)間進(jìn)行評(píng)價(jià),對(duì)不同時(shí)間點(diǎn)的T2值結(jié)果進(jìn)行student t檢驗(yàn)。 結(jié)果(1)成功制備了油酸鈉-SPIOs、殼聚糖-SPIOs和葡聚糖-SPIOs三種磁流體。(2)激光衍射粒度分析和透射電鏡檢測(cè)結(jié)果顯示SPIOs粒子均勻度好,粒徑為10-20nm左右的類球形結(jié)晶。(3)振蕩磁強(qiáng)計(jì)檢測(cè)結(jié)果顯示:油酸鈉、殼聚糖、葡聚糖修飾的SPIOs均具有超順磁性質(zhì)。(4)大鼠一般情況好,給藥及觀察期間未發(fā)生死亡。(5)各實(shí)驗(yàn)組血清中的肝腎功血生化指標(biāo)僅油酸鈉SPIOs組第1天TP含量和第14天ALP含量高于對(duì)照組,其他主要血生化指標(biāo)各實(shí)驗(yàn)組與對(duì)照組比較無統(tǒng)計(jì)學(xué)差異(P0.05)。(6)大鼠尾靜脈注射SPIOs后10min磁共振掃描結(jié)果顯示三種不同修飾材料的SPIOs均能顯著降低肝臟信號(hào),但殼聚糖修飾的SPIOs降低肝臟信號(hào)更明顯。(7)大鼠尾靜脈注射相同濃度的三種相似粒徑不同修飾材料的SPIOs磁共振增強(qiáng)掃描,均能明顯縮短T2弛豫時(shí)間,不同時(shí)間點(diǎn)T2值先降低后升高,殼聚糖組下降最快,約30min達(dá)最低峰值,三組峰值無明顯差異,約6h殼聚糖組和葡聚糖組T2值明顯上升,而油酸鈉T2值雖有上升但與另外兩組有顯著性差異。縮短T2弛豫時(shí)間各組與對(duì)照組差異有顯著性意義(P0.05),達(dá)峰時(shí)間殼聚糖組與另兩組間有顯著性意義(P0.05)。 結(jié)論油酸鈉、殼聚糖和葡聚糖Fe3O4納米粒均具有超順磁性能,且對(duì)大鼠無明顯急性毒性;油酸鈉、殼聚糖和葡聚糖修飾的SPIOs均能縮短T2弛豫時(shí)間,引起磁共振信號(hào)的變化;其中殼聚糖修飾的SPIOs降低磁共振信號(hào)最明顯,T2值達(dá)峰值時(shí)間最短,體內(nèi)清除速率快等優(yōu)點(diǎn),因此殼聚糖被認(rèn)為是較好的表面修飾材料。
[Abstract]:Objective to prepare superparamagnetic ferric trioxide nanoparticles modified with sodium oleate (sodium oleate), chitosan (chitosan) and dextran (dextran), and characterize them to study their acute toxicity to rats and evaluate their imaging effects as magnetic resonance contrast agents. To provide experimental basis for further optimization of magnetic resonance contrast agent formulation. Methods (1) Sodium oleate, chitosan and dextran were synthesized by chemical coprecipitation method. The morphology and structure of SPIOsS were observed by laser diffraction analyzer, transmission electron microscope and vibratory magnetometer. (2) 72 SD rats were randomly divided into three groups: saline control group, sodium oleate SPIOs group, chitosan SPIOs group and dextran SPIOs group. At a dose of 100 渭 mol / kg, the general situation of rats was observed and recorded. Six rats in each group were randomly killed on day 1, day 3 and day 14 after administration of the drug. (3) 32 SD rats were randomly divided into three groups: saline control group, sodium oleate SPIOs group, chitosan SPIOs group and dextran SPIOs group. The relaxation time of different modified materials was evaluated by using 3-inch coil SE T2map-FRFSE T2WI sequence, and the T _ 2 value of different time points was tested by student t test, respectively, at 10 min, 30 min, 60 min and 3 h after administration on GE 1.5T magnetic resonance scanner, and the results of T _ 2 T _ 2 T _ 2WI were tested by student t test. The relaxation time of different modified materials was evaluated by FRFSE T _ 2WI, and the results of T _ 2 at different time points were examined by student t test. Results (1) three kinds of magnetofluids, sodium oleate, chitosan SPIOs and dextran SPIOs, were successfully prepared. (2) the results of laser diffraction and transmission electron microscopy showed that the uniformity of SPIOs particles was good. (3) the results of oscillatory magnetometer showed that sodium oleate, chitosan and dextran modified SPIOs had superparamagnetic properties. (4) the rats were in good condition. No death occurred during administration and observation. (5) the serum biochemical indexes of liver and kidney function in each experimental group were only higher than those in control group on day 1 and day 14 in sodium oleate SPIOs group. There was no significant difference in other blood biochemical indexes between the experimental group and the control group (P0.05). (6). The results of 10min magnetic resonance imaging showed that the three kinds of modified materials could significantly reduce the liver signal after injection of SPIOs into the tail vein of rats. However, chitosan modified SPIOs decreased liver signal more significantly. (7) SPIOs enhanced scanning with the same concentration of three kinds of materials with the same particle size and different modified materials significantly shortened the T 2 relaxation time. At different time points, T2 value decreased first and then increased. In chitosan group, the decrease was the fastest, about 30min reached the lowest peak value, and there was no significant difference among the three groups. The T2 value of chitosan group and dextran group increased significantly at about 6 h. The T 2 value of sodium oleate was higher than that of the other two groups. There was significant difference in T _ 2 relaxation time between the two groups (P0.05), and significant difference between the chitosan group and the other two groups (P0.05). Conclusion Sodium oleate, chitosan and dextran Fe _ 3O _ 4 nanoparticles have superparamagnetic energy and no acute toxicity to rats, sodium oleate, chitosan and dextran modified SPIOs can shorten T2 relaxation time and cause magnetic resonance signal change. Chitosan modified SPIOs is considered to be a good surface modification material because it has the advantages of the shortest time to reduce the peak T _ 2 value of magnetic resonance signal and the faster clearance rate in vivo.
【學(xué)位授予單位】:重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類號(hào)】:R445.2

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