自制纳米微泡造影剂的特性及裸鼠体内造影增强实验的研究

发布时间：2018-03-27 11:03

本文选题：纳米　切入点：微泡造影剂　出处：《山西医科大学》2017年硕士论文

【摘要】：目的:本研究通过探测自主研制的纳米超声造影剂的体外物理特征及其与微米级造影剂在裸鼠体内的显影效果的定量对比分析,探讨纳泡在肿瘤诊断及临床应用方面的价值。方法:应用机械振动法制备纳泡,观察纳泡的形态、分布,检测初始纳泡的粒径大小、电位以及浓度,纳泡在无菌环境下保存2周后,观察粒径大小等体外物理性质较刚制备时有无变化;构建裸鼠膀胱癌移植瘤模型,通过尾静脉注射纳米级造影剂150μl/只,2h以后同样的方法注射声诺维Sonovue造影剂150μl/只,存储动态造影图像,采用自身前后对照的统计学方法观察两种造影剂在裸鼠体内的成像特征以及相关定量参数的差异性。结果:(1)镜下纳泡接近圆形,大小、分布较均匀,离散度较好。纳泡的粒径范围在418-490nm之间,平均粒径463.20±27.69nm(n=5),表面电荷-14.80±1.26mV,浓度约为(2.42±0.12)x108/ml,4℃冰箱中保存1周后,平均粒径525.80±18.08nm(n=5),浓度(2.23±0.10)x108/ml,较1周前对比无统计学差异(P0.05);10d后,纳泡表面电位-13.94±0.23mv,较刚制备时对比无统计学差异(P0.05)。(2)纳米级造影剂能明显增强瘤体的灰阶显像,纳泡组造影剂到达时间(0.90±0.42s)和达峰时间(24.01±5.83s)较微泡组(0.35±0.15s、2.91±0.93s)晚,峰值持续时间(111.65±20.87s)较微泡组(58.59±10.49s)长,但峰值强度(14.18±3.45dB)较微泡组(19.36±3.72dB)弱,上升支斜率(1.37±0.15)较微泡组(6.16±0.54)慢,两者比较差异均有统计学意义(均P0.05),纳泡组上升支曲线下面积(59.58±14.67)与微泡组(52.52±15.93)比较无统计学差异(P=0.443)。(3)纳泡组与微泡组的衰减斜率分别是-1.60±0.36dB/s、-3.42±0.21dB/s(P0.05),两组斜率的比值称为衰减斜率比率(decay-slope ratio,DSR),DSR=2.14,微泡的清除率比纳泡快2.14倍。两组在10s,20s,90s,2min,4min,8min这几个时间点对应的瘤体灰阶值比较均有统计学差异(P0.05),两组造影剂的时间强度曲线在50s左右存在交叉。结论:自制纳米级造影剂粒径小,镜下大小、分布较匀称,离散度较好,体外性质稳定,为标准规范纳泡的制备方法提供了依据;纳泡在裸鼠体内能够使瘤体显影,与常规造影剂比较,效果明显,有一定的临床应用价值,为靶性纳米造影剂的进一步制备及研究奠定了一定的基础。
[Abstract]:Objective: to investigate the physical characteristics of nano-ultrasound contrast agent and its quantitative comparison with micron contrast agent in nude mice. Methods: the morphology and distribution of the vesicles were observed, and the particle size, potential and concentration of the initial vesicles were measured. After preservation in aseptic environment for 2 weeks, the in vitro physical properties such as particle size were observed. In the same way, 150 渭 l of sonovir Sonovue contrast agent was injected into the tail vein of 150 渭 l / 2 h later, and the dynamic contrast images were stored. The imaging characteristics of the two contrast agents in nude mice and the difference of quantitative parameters were observed by using the statistical method of self-control before and after. Results under the microscope, the vesicles were round, large and evenly distributed. The average particle size was 463.20 卤27.69 nm ~ 5g / ml, the surface charge was -14.80 卤1.26 MV, the concentration was about 2.42 卤0.12 脳 10 ~ 8 / ml ~ (-1) C refrigerator for 1 week, the average diameter was 525.80 卤18.08 nm ~ 5ml, and the concentration was 2.23 卤0.10 ~ (10) n ~ (-1) 脳 10 ~ (-8) ml. There was no significant difference between the two groups after 10 days. Nanovesicular surface potential (-13.94 卤0.23 MV) showed no statistical difference compared with that at the time of preparation. Nanometer contrast agents could significantly enhance the gray scale imaging of the tumor. The arrival time of the contrast medium and the peak time (24.01 卤5.83 s) in the bubble group were significantly higher than those in the microbubble group (0.35 卤0.15 seconds, 2.91 卤0.93s), and the peak time was 24.01 卤5.83 seconds later than that in the microbubble group, and the time of arrival (0.90 卤0.42s) and the peak time (24.01 卤5.83s) were higher in the bubble group than in the microbubble group. The peak duration (111.65 卤20.87s) was longer than that of the microbubble group (58.59 卤10.49s), but the peak intensity was 14.18 卤3.45dB) weaker than that of the microbubble group (19.36 卤3.72dB), and the slope of ascending branch was 1.37 卤0.15), which was slower than that of the microbubble group (6.16 卤0.54). There was no significant difference between the two groups (P 0.05, the area under the ascending branch curve was 59.58 卤14.67) and that in the microbubble group was 52.52 卤15.93). The slope of attenuation between the two groups was -1.60 卤0.36 dB / s -3.42 卤0.21 dB / s P 0.05, respectively. The slope ratio of the two groups was called oblique attenuation. The clearance rate of microbubbles was 2.14 times faster than that of NAB. There were significant differences in the gray scale of tumor between the two groups at the time points of 10 s ~ 20 s ~ 20 s ~ 90 s ~ 2 min ~ 4 min ~ 8 min ~ 8 min ~ 8 min. The time intensity curves of the two groups were crossed in 50 s. The size of nano-scale contrast agent made by ourselves is small, The size, distribution, dispersion, stability in vitro and size under microscope provide the basis for the standard standard preparation method of nano-bubble, which can make the tumor develop in nude mice, and the effect is obvious compared with the conventional contrast medium. It has certain clinical application value and lays a certain foundation for the further preparation and research of target nano-contrast agent.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R445.1

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