MRI引导聚焦超声开放血脑屏障靶向传递不同分子数量级药物的研究

发布时间：2018-10-10 10:48

【摘要】：探讨MRI引导聚焦超声开放兔血脑屏障(BBB)后药物在脑内的摄入量与药物分子量之间的关系及药物在靶区空间分布情况。25只新西兰大白兔被随机平均分为5组,在MRI引导聚焦超声开放BBB后,分别静脉注入荧光标记的不同分子数量级的右旋糖酐(10,150 and 2000 k Da),采用激光共聚焦显微镜检测其在靶区的荧光强度,并将切片行免疫荧光染色观察右旋糖酐与神经元标志物共区域化现象。10k Da的右旋糖酐以最高浓度呈片状分布在整个超声照射区域,而150 k Da和2000 k Da的右旋糖酐以较低的浓度在靶区呈点状分布(P0.01);通过与神经元标志物共区域化,10k Da的右旋糖酐更为均一的分布在整个神经元胞浆和胞核内,而150 k Da和2000 k Da的右旋糖酐在神经元胞浆内主要以囊泡样结构分布,且后者该结构的数量较少。MRI引导聚焦超声开放BBB后,药物在脑内的摄入量与药物分子量有关,分子量越小靶区药物浓度越高,其在神经元内的分布越均一。本研究将有助于治疗脑部疾病药物的合理设计、选择和应用。
[Abstract]:To investigate the relationship between drug intake and molecular weight of blood brain barrier (BBB) after (BBB) was opened by MRI guided focused ultrasound. Twenty-five New Zealand white rabbits were randomly divided into 5 groups. After BBB was opened by MRI guided focused ultrasound, fluorescence labeled dextran (10150 and 2000 k Da),) was injected intravenously to detect its fluorescence intensity in the target region by laser confocal microscopy. Immunofluorescence staining was performed to observe the distribution of dextran with neuronal markers. 10 k Da dextran in the whole ultrasound irradiated area with the highest concentration. The dextran of 150k Da and 2000 k Da distributed in the target region at lower concentration (P0.01), and the dextran distributed more uniformly in the whole neuron cytoplasm and nucleus by co-regionalizing the dextran of 10k Da with the neuronal marker. The concentration of dextran at 150k Da and 2000 k Da was mainly vesicular structure in the cytoplasm of neurons, and the quantity of the latter structure was less. The intake of dextran in the brain was related to the molecular weight of drug after the BBB was opened by focused ultrasound. The smaller the molecular weight, the higher the concentration of the drug, the more uniform the distribution in neurons. This study will be helpful to the rational design, selection and application of drugs for treating brain diseases.
【作者单位】：重庆医科大学第二附属医院神经外科;重庆医科大学生物医学工程研究院;
【基金】：国家自然科学基金(81371674和81401505)资助课题
【分类号】：R965

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