本文選題：納米　切入點(diǎn)：微泡造影劑　出處：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:本研究通過探測(cè)自主研制的納米超聲造影劑的體外物理特征及其與微米級(jí)造影劑在裸鼠體內(nèi)的顯影效果的定量對(duì)比分析,探討納泡在腫瘤診斷及臨床應(yīng)用方面的價(jià)值。方法:應(yīng)用機(jī)械振動(dòng)法制備納泡,觀察納泡的形態(tài)、分布,檢測(cè)初始納泡的粒徑大小、電位以及濃度,納泡在無菌環(huán)境下保存2周后,觀察粒徑大小等體外物理性質(zhì)較剛制備時(shí)有無變化;構(gòu)建裸鼠膀胱癌移植瘤模型,通過尾靜脈注射納米級(jí)造影劑150μl/只,2h以后同樣的方法注射聲諾維Sonovue造影劑150μl/只,存儲(chǔ)動(dòng)態(tài)造影圖像,采用自身前后對(duì)照的統(tǒng)計(jì)學(xué)方法觀察兩種造影劑在裸鼠體內(nèi)的成像特征以及相關(guān)定量參數(shù)的差異性。結(jié)果:(1)鏡下納泡接近圓形,大小、分布較均勻,離散度較好。納泡的粒徑范圍在418-490nm之間,平均粒徑463.20±27.69nm(n=5),表面電荷-14.80±1.26mV,濃度約為(2.42±0.12)x108/ml,4℃冰箱中保存1周后,平均粒徑525.80±18.08nm(n=5),濃度(2.23±0.10)x108/ml,較1周前對(duì)比無統(tǒng)計(jì)學(xué)差異(P0.05);10d后,納泡表面電位-13.94±0.23mv,較剛制備時(shí)對(duì)比無統(tǒng)計(jì)學(xué)差異(P0.05)。(2)納米級(jí)造影劑能明顯增強(qiáng)瘤體的灰階顯像,納泡組造影劑到達(dá)時(shí)間(0.90±0.42s)和達(dá)峰時(shí)間(24.01±5.83s)較微泡組(0.35±0.15s、2.91±0.93s)晚,峰值持續(xù)時(shí)間(111.65±20.87s)較微泡組(58.59±10.49s)長,但峰值強(qiáng)度(14.18±3.45dB)較微泡組(19.36±3.72dB)弱,上升支斜率(1.37±0.15)較微泡組(6.16±0.54)慢,兩者比較差異均有統(tǒng)計(jì)學(xué)意義(均P0.05),納泡組上升支曲線下面積(59.58±14.67)與微泡組(52.52±15.93)比較無統(tǒng)計(jì)學(xué)差異(P=0.443)。(3)納泡組與微泡組的衰減斜率分別是-1.60±0.36dB/s、-3.42±0.21dB/s(P0.05),兩組斜率的比值稱為衰減斜率比率(decay-slope ratio,DSR),DSR=2.14,微泡的清除率比納泡快2.14倍。兩組在10s,20s,90s,2min,4min,8min這幾個(gè)時(shí)間點(diǎn)對(duì)應(yīng)的瘤體灰階值比較均有統(tǒng)計(jì)學(xué)差異(P0.05),兩組造影劑的時(shí)間強(qiáng)度曲線在50s左右存在交叉。結(jié)論:自制納米級(jí)造影劑粒徑小,鏡下大小、分布較勻稱,離散度較好,體外性質(zhì)穩(wěn)定,為標(biāo)準(zhǔn)規(guī)范納泡的制備方法提供了依據(jù);納泡在裸鼠體內(nèi)能夠使瘤體顯影,與常規(guī)造影劑比較,效果明顯,有一定的臨床應(yīng)用價(jià)值,為靶性納米造影劑的進(jìn)一步制備及研究奠定了一定的基礎(chǔ)。
[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 鹵27.69 nm ~ 5g / ml, the surface charge was -14.80 鹵1.26 MV, the concentration was about 2.42 鹵0.12 脳 10 ~ 8 / ml ~ (-1) C refrigerator for 1 week, the average diameter was 525.80 鹵18.08 nm ~ 5ml, and the concentration was 2.23 鹵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 鹵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 鹵5.83 s) in the bubble group were significantly higher than those in the microbubble group (0.35 鹵0.15 seconds, 2.91 鹵0.93s), and the peak time was 24.01 鹵5.83 seconds later than that in the microbubble group, and the time of arrival (0.90 鹵0.42s) and the peak time (24.01 鹵5.83s) were higher in the bubble group than in the microbubble group. The peak duration (111.65 鹵20.87s) was longer than that of the microbubble group (58.59 鹵10.49s), but the peak intensity was 14.18 鹵3.45dB) weaker than that of the microbubble group (19.36 鹵3.72dB), and the slope of ascending branch was 1.37 鹵0.15), which was slower than that of the microbubble group (6.16 鹵0.54). There was no significant difference between the two groups (P 0.05, the area under the ascending branch curve was 59.58 鹵14.67) and that in the microbubble group was 52.52 鹵15.93). The slope of attenuation between the two groups was -1.60 鹵0.36 dB / s -3.42 鹵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.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R445.1

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