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学科主题: 放射科学
题名:
基于脑局部给药的药物分布与清除大鼠模型的建立
其他题名: Establishment of a Rat Model of Drug Distribution and Clearance for Brain Localized Delivery
作者: 左龙; 雷易鸣; 闫军浩; 刘会坡; 袁兰; 蒲小平; 韩鸿宾
关键词: 组织间液 ; 细胞外间隙 ; 示踪剂 ; 扩散 ; Brain interstitial fluid ; Interstitial space ; Tracer ; Water diffusion
刊名: 中国微创外科杂志
发表日期: 2015
DOI: 10.3969/j.issn.1009-6604.2015.04.023
期: 4, 页:360-365
收录类别: 中国科技核心期刊 ; CSCD
文章类型: Journal Article
摘要: 目的:应用磁共振分子探针示踪技术,研究大鼠深部脑组织间隙( interstitial space,ISS)内物质转运与脑组织液引流的规律。结合多孔介质经典扩散方程,建立大鼠脑局部给药的药物分布与清除动力学模型。方法24只SD大鼠随机分为尾状核、丘脑、中脑黑质3组(n=8)。将细胞外示踪剂惰性分子探针钆喷酸葡胺(gadolinium-diethylenetriaminepentaacetic acid,Gd-DTPA)2μl分别导入三个脑区细胞外间隙,利用磁共振成像( MRI)动态采集探针在大鼠脑ISS内的分布与清除过程。通过图像后处理获取ISS内示踪分子在大鼠全脑分布的最大分布容积比( Vdmax%)及半衰期( t1/2)。应用经典扩散方程,测量ISS有效扩散系数( D*)、清除率( k’)与局部迂曲度(λ)。结合上述结果及经典扩散方程,建立大鼠脑组织间隙内药代动力模型。结果示踪分子在大鼠不同脑区ISS内的转运分布区域、清除速率各不相同。尾状核Vdmax%和t1/2大于丘脑和黑质(P=0.000)。黑质区D*小于尾状核、丘脑(P=0.021),黑质ISS内迂曲度最大(P=0.280)。丘脑局部k’大于尾状核和黑质区域(P=0.000)。结论钆喷酸葡胺(Gd-DTPA)在大鼠深部脑组织内分布呈分区特征,各分区内药物的分布与清除速率各不相同。脑局部给药需考虑脑内ISS的解剖分区以及各个脑分区的物质转运与脑组织液流动参数特征。 Objective To explore the drainage process of brain interstitial fluid ( ISF) and transport property in interstitial space ( ISS) in rat deep brain tissue by tracer-based magnetic resonance imaging ( MRI) .On the basis of classical diffusion equation in porous media , to establish distribution and clearance model for local drug administration of brain . Methods A total of 24 Sprague Dawley rats were randomly divided into three groups according to the injection points : caudate putamen (CPu), thalamus (T), and substantia nigra ( SN ) , with 8 rats in each group . The brain ISF was traced with a MRI contrast agent , 2 μl gadolinium diethylenetriaminepentaacetic acid ( Gd-DTPA) , which was injected into the brain ISS .Three-dimensional dynamic distribution of the probes was displayed and quantitative calculations were completed by self -developed image processing software .The distribution ratio referring tracers’ maximum volume of the whole brain (Vdmax%) and the half-life time (t1/2) were obtained.ISS microscopic diffusion parameter (D*), clearance rate (k’), and local tortuosity (λ) were measured based on classical diffusion equation .Hence, we established pharmacokinetics model of the brain ISS . Results The transport distribution area and clearance rates of tracer molecule varied in ISS of different brain regions .The Vdmax% and t1/2 of the caudate putamen were greater than those of the thalamus and substantia nigra (P=0.000).The D*in substantia nigra was less than that in caudate putamen and thalamus (P=0.021), deriving the greatest λin substantia nigra (P=0.280).The k’ in thalamus was greater than that in caudate putamen and substantia nigra (P=0.000). Conclusions Drug distribution in the brain ISS is partitioned , with drug distribution and clearance rates varyingwithin each sub-region.Topical brain anatomy in each brain partition and fluid flow parameter characteristics of partitioned ISS should be considered in local brain delivery .
语种: 中文
原文出处: 查看原文
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/69392
Appears in Collections:北京大学第三临床医学院_放射科_期刊论文

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作者单位: 1.北京大学第三医院放射科 磁共振成像设备与技术北京市重点实验室,北京,100191
2.北京大学信息科学技术学院,北京,100871
3.北京大学医学部基础医学院,北京,100191
4.北京应用物理与计算数学研究所,北京,100088
5.北京大学医药卫生分析中心,北京,100191
6.北京大学药学院,北京,100191

Recommended Citation:
左龙,雷易鸣,闫军浩,等. 基于脑局部给药的药物分布与清除大鼠模型的建立[J]. 中国微创外科杂志,2015(4):360-365.
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