三种磁性纳米粒子作为MRI对比剂的探索研究

发布时间：2018-06-22 15:49

本文选题：SPIOs + 油酸钠　；参考：《重庆医科大学》2014年硕士论文

【摘要】：目的制备油酸钠(sodium oleate)、壳聚糖(chitosan)和葡聚糖（dextran）修饰的超顺磁性四氧化三铁纳米粒（SPIOs），并对其进行表征，研究其对大鼠的急性毒性效应，评估其作为磁共振对比剂的成像效果，为进一步优化磁共振对比剂配方提供实验基础。方法（1）化学共沉淀法合成油酸钠、壳聚糖和葡聚糖三种不同表面修饰的SPIOs，通过激光衍射分析仪，透射电镜及振动磁强计对其进行形貌结构观察、粒径分布和磁性性能表征。（2）选用SD大鼠72只，随机分为生理盐水对照组、油酸钠-SPIOs组、壳聚糖-SPIOs组和葡聚糖-SPIOs组，10%水合氯醛腹腔麻醉后尾静脉给药，剂量100μmol/kg，对大鼠的一般情况进行观察记录，于给药后第1天、第3天和第14天随机处死每组中6只大鼠，腹腔静脉取血检测肝肾功血生化指标。（3）选用SD大鼠32只随机分为生理盐水对照组、油酸钠-SPIOs组、壳聚糖-SPIOs组和葡聚糖-SPIOs组，10%水合氯醛腹腔麻醉后尾静脉给药，，分别于给药后10min、30min、60min、3h、6h在GE1.5T磁共振扫描仪上进行扫描，采用3英寸线圈，SE T2map、FRFSE T2WI序列扫描，对应用不同修饰材料SPIOs时的弛豫时间进行评价，对不同时间点的T2值结果进行student t检验。结果（1）成功制备了油酸钠-SPIOs、壳聚糖-SPIOs和葡聚糖-SPIOs三种磁流体。(2)激光衍射粒度分析和透射电镜检测结果显示SPIOs粒子均匀度好，粒径为10-20nm左右的类球形结晶。(3)振荡磁强计检测结果显示：油酸钠、壳聚糖、葡聚糖修饰的SPIOs均具有超顺磁性质。（4）大鼠一般情况好，给药及观察期间未发生死亡。(5)各实验组血清中的肝肾功血生化指标仅油酸钠SPIOs组第1天TP含量和第14天ALP含量高于对照组，其他主要血生化指标各实验组与对照组比较无统计学差异(P0.05)。（6）大鼠尾静脉注射SPIOs后10min磁共振扫描结果显示三种不同修饰材料的SPIOs均能显著降低肝脏信号，但壳聚糖修饰的SPIOs降低肝脏信号更明显。（7）大鼠尾静脉注射相同浓度的三种相似粒径不同修饰材料的SPIOs磁共振增强扫描，均能明显缩短T2弛豫时间，不同时间点T2值先降低后升高，壳聚糖组下降最快，约30min达最低峰值，三组峰值无明显差异，约6h壳聚糖组和葡聚糖组T2值明显上升，而油酸钠T2值虽有上升但与另外两组有显著性差异。缩短T2弛豫时间各组与对照组差异有显著性意义(P0．05），达峰时间壳聚糖组与另两组间有显著性意义(P0．05）。结论油酸钠、壳聚糖和葡聚糖Fe3O4纳米粒均具有超顺磁性能，且对大鼠无明显急性毒性；油酸钠、壳聚糖和葡聚糖修饰的SPIOs均能缩短T2弛豫时间，引起磁共振信号的变化；其中壳聚糖修饰的SPIOs降低磁共振信号最明显，T2值达峰值时间最短，体内清除速率快等优点，因此壳聚糖被认为是较好的表面修饰材料。
[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.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R445.2

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