光、磁分子探针在脑组织间隙内的扩散分布规律
发布时间：2019-03-27 07:23
【摘要】：目的:对比荧光分子探针四甲基罗丹明-葡聚糖(dextran-tetramethylrhodamine,DT)和荧光黄(lucifer yellow CH,LY)、磁性分子探针钆-二乙三胺五乙酸(gadolinium-diethylene triamine pentaacetic acid,Gd-DTPA)在多孔介质中的动态扩散分布规律,筛选合适的荧光分子探针用于大鼠脑组织间隙(interstitial space,ISS)光学成像。方法:琼脂糖凝胶分为DT组、LY组、Gd-DTPA组,分别导入相应分子探针,应用激光扫描共聚焦显微镜分别动态观察DT、LY在琼脂糖凝胶内的扩散分布,与磁共振成像显示的Gd-DTPA在琼脂糖凝胶内的动态扩散过程进行比较。LY分别导入18只大鼠尾状核,对不同时间点离体脑切片进行荧光成像,其成像数据与相应导入Gd-DTPA的大鼠的磁共振在体检测成像数据进行对比。结果:DT、LY及Gd-DTPA在琼脂糖凝胶中的扩散分布均表现为各向同性,平均扩散分布速率分别为:(0.07±0.02)×10-2mm2/s、(1.54±0.47)×10-2mm2/s、(1.45±0.50)×10-2mm2/s,DT与LY、DT与Gd-DTPA间差异均有统计学意义(ANOVA,F=367.15,P0.001;Post-Hoc LSD,P0.001),LY与Gd-DTPA间差异无统计学意义(Post-Hoc LSD,P=0.091)。重复测量方差分析比较分子探针的扩散分布面积随时间变化的趋势:DT与LY、DT与Gd-DTPA间的变化规律差异均有统计学意义(Bonferroni校正,α=0.0125,P0.001),LY与Gd-DTPA间差异无统计学意义(Bonferroni校正,α=0.0125,P=0.203)。LY与Gd-DTPA在大鼠尾状核ISS内分布随时间变化呈各向异性,均表现为指向同侧皮层区的单方向楔形扩散,平均扩散分布速率分别为(1.03±0.29)×10-3mm2/s和(0.81±0.27)×10-3mm2/s,t=0.759,P=0.490;信号衰减半衰期分别为(2.58±0.04)h和(2.46±0.10)h,t=2.025,P=0.113。LY与Gd-DTPA间扩散分布面积比率在0.5、1、2、3、7 h差异无统计学意义(t=2.249,P=0.088;t=2.582,P=0.061;t=1.966,P=0.121;t=0.132,P=0.674;t=0.032,P=0.976),在11 h差异有统计学意义(t=2.917,P=0.043)。结论:LY与Gd-DTPA在多孔介质内的扩散分布规律一致,是ISS荧光成像的适用分子探针,可用于脑ISS的微观、宏观、离体检测。
[Abstract]:Objective: to compare the fluorescence molecular probes, tetramethylrhodamine-dextran (dextran-tetramethylrhodamine,DT) and fluorescent yellow (lucifer yellow CH,LY, and magnetic molecular probes, gadolinium-diethyltriamine pentaacetic acid (gadolinium-diethylene triamine pentaacetic acid,). The dynamic diffusion distribution of Gd-DTPA in porous media was studied. A suitable fluorescent molecular probe was selected for optical imaging of rat brain tissue gap (interstitial space,ISS). Methods: agarose gels were divided into three groups: DT group, LY group and Gd-DTPA group. The diffusion distribution of DT,LY in agarose gel was observed dynamically by laser scanning confocal microscope. The dynamic diffusion process of Gd-DTPA in agarose gel was compared with magnetic resonance imaging (MRI). LY was introduced into the caudate nucleus of 18 rats, and fluorescence imaging was performed on brain slices at different time points. The imaging data were compared with the magnetic resonance imaging (MRI) data of the rats introduced into Gd-DTPA. Results: the diffusion distribution of DT,LY and Gd-DTPA in agarose gel was isotropic, and the average diffusion rates were (0.07 卤0.02) 脳 10 脳 10 ~ (2) mm ~ (2) vs (1.54 卤0.47) 脳 10 ~ (2) mm ~ (2 / s), respectively. (1.45 卤0.50) 脳 10 ~ (2) mm ~ (2), there was significant difference between DT and LY,DT and Gd-DTPA (ANOVA,F=367.15,P0.001;). There was no significant difference between Post-Hoc LSD,P0.001), LY and Gd-DTPA (Post-Hoc LSD,P=0.091). The variation trend of diffusion distribution area of molecular probe with time was compared by repeated measurement of variance analysis. The difference between DT and LY,DT and Gd-DTPA was statistically significant (Bonferroni correction, 伪 = 0.0125, P0.001), and the difference was statistically significant between the two groups (Bonferroni correction, 伪 = 0.0125, P0.001). There was no significant difference between LY and Gd-DTPA (Bonferroni correction, 伪 = 0.0125, P = 0.203). The distribution of LY and Gd-DTPA in the caudate nucleus ISS of rats showed anisotropy with time, which showed that the distribution of LY and Gd-DTPA was one-way wedge diffusion pointing to the ipsilateral cortex. The average diffusion rates were (1.03 卤0.29) 脳 10-3mm2/s and (0.81 卤0.27) 脳 10 脳 10 ~ (3) mm ~ (2 / s), t = 0.759, P = 0.490, respectively. The half-life of signal attenuation was (2.58 卤0.04) h and (2.46 卤0.10) h, t = 2.025, P = 0.113.LY / Gd-DTPA was 0.5,1,2,3 and 7 h, respectively, and there was no significant difference between them (t = 2.249, P = 0.088). T = 2.582, P = 0.061 / t / 1.966, P = 0.121 / t / 0.132, P = 0.674 / t / 0.032, P = 0.976), and there was a significant difference at 11 h (t = 2.917, P = 0.043). Conclusion: the diffusion distribution of LY and Gd-DTPA in porous media is consistent, and it is a suitable molecular probe for ISS fluorescence imaging. It can be used for microcosmic, macroscopical and in vitro detection of brain ISS.
【作者单位】： 大连大学环境与化学工程学院;北京大学医药卫生分析中心;北京市磁共振成像设备与技术重点实验室;北京大学第三医院放射科;北京大学第三医院神经科;北京大学第三医院临床流行病学研究中心;
【基金】：国家自然科学基金(61450004;91330103) 北京市科技专项(z141107004414031) 高等学校博士学科点专项科研基金(20130001130013)资助~~
【分类号】：R445.2
[Abstract]:Objective: to compare the fluorescence molecular probes, tetramethylrhodamine-dextran (dextran-tetramethylrhodamine,DT) and fluorescent yellow (lucifer yellow CH,LY, and magnetic molecular probes, gadolinium-diethyltriamine pentaacetic acid (gadolinium-diethylene triamine pentaacetic acid,). The dynamic diffusion distribution of Gd-DTPA in porous media was studied. A suitable fluorescent molecular probe was selected for optical imaging of rat brain tissue gap (interstitial space,ISS). Methods: agarose gels were divided into three groups: DT group, LY group and Gd-DTPA group. The diffusion distribution of DT,LY in agarose gel was observed dynamically by laser scanning confocal microscope. The dynamic diffusion process of Gd-DTPA in agarose gel was compared with magnetic resonance imaging (MRI). LY was introduced into the caudate nucleus of 18 rats, and fluorescence imaging was performed on brain slices at different time points. The imaging data were compared with the magnetic resonance imaging (MRI) data of the rats introduced into Gd-DTPA. Results: the diffusion distribution of DT,LY and Gd-DTPA in agarose gel was isotropic, and the average diffusion rates were (0.07 卤0.02) 脳 10 脳 10 ~ (2) mm ~ (2) vs (1.54 卤0.47) 脳 10 ~ (2) mm ~ (2 / s), respectively. (1.45 卤0.50) 脳 10 ~ (2) mm ~ (2), there was significant difference between DT and LY,DT and Gd-DTPA (ANOVA,F=367.15,P0.001;). There was no significant difference between Post-Hoc LSD,P0.001), LY and Gd-DTPA (Post-Hoc LSD,P=0.091). The variation trend of diffusion distribution area of molecular probe with time was compared by repeated measurement of variance analysis. The difference between DT and LY,DT and Gd-DTPA was statistically significant (Bonferroni correction, 伪 = 0.0125, P0.001), and the difference was statistically significant between the two groups (Bonferroni correction, 伪 = 0.0125, P0.001). There was no significant difference between LY and Gd-DTPA (Bonferroni correction, 伪 = 0.0125, P = 0.203). The distribution of LY and Gd-DTPA in the caudate nucleus ISS of rats showed anisotropy with time, which showed that the distribution of LY and Gd-DTPA was one-way wedge diffusion pointing to the ipsilateral cortex. The average diffusion rates were (1.03 卤0.29) 脳 10-3mm2/s and (0.81 卤0.27) 脳 10 脳 10 ~ (3) mm ~ (2 / s), t = 0.759, P = 0.490, respectively. The half-life of signal attenuation was (2.58 卤0.04) h and (2.46 卤0.10) h, t = 2.025, P = 0.113.LY / Gd-DTPA was 0.5,1,2,3 and 7 h, respectively, and there was no significant difference between them (t = 2.249, P = 0.088). T = 2.582, P = 0.061 / t / 1.966, P = 0.121 / t / 0.132, P = 0.674 / t / 0.032, P = 0.976), and there was a significant difference at 11 h (t = 2.917, P = 0.043). Conclusion: the diffusion distribution of LY and Gd-DTPA in porous media is consistent, and it is a suitable molecular probe for ISS fluorescence imaging. It can be used for microcosmic, macroscopical and in vitro detection of brain ISS.
【作者单位】： 大连大学环境与化学工程学院;北京大学医药卫生分析中心;北京市磁共振成像设备与技术重点实验室;北京大学第三医院放射科;北京大学第三医院神经科;北京大学第三医院临床流行病学研究中心;
【基金】：国家自然科学基金(61450004;91330103) 北京市科技专项(z141107004414031) 高等学校博士学科点专项科研基金(20130001130013)资助~~
【分类号】：R445.2
【参考文献】
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