北京大学学报(医学版) ›› 2020, Vol. 52 ›› Issue (2): 362-367. doi: 10.19723/j.issn.1671-167X.2020.02.026
宋宇1,2,韩鸿宾2,3,4,△(),杨军5,王艾博3,4,和清源3,4,李媛媛3,4,赵国梅3,4,高亚娟3,4,王睿3,4,韩易兴3,4,刘爱连1,△(),宋清伟1,△()
Yu SONG1,2,Hong-bin HAN2,3,4,△(),Jun YANG5,Ai-bo WANG3,4,Qing-yuan HE3,4,Yuan-yuan LI3,4,Guo-mei ZHAO3,4,Ya-juan GAO3,4,Rui WANG3,4,Yi-xing HAN3,4,Ai-lian LIU1,△(),Qing-wei SONG1,△()
摘要:
目的 对比研究经细胞外间隙(extracellular space,ECS)途径的脑对流增强给药(convection enhanced delivery, CED)在进行脑病微创治疗时,不同给药速率下成年大鼠与老年大鼠脑ECS结构参数及局部药物分布的改变.方法: 36只SD雄性大鼠按照月龄分为成年大鼠组(2~8月龄,18只)和老年大鼠组(18~24月龄,18只),每组再按照不同的给药速率(0.1 μL/min,0.2 μL/min,0.3 μL/min)随机分为3个亚组,每亚组6只.采用立体定位注射法分别在各组鼠脑尾状核区导入浓度为10 mmol/L的磁示踪剂钆-二乙三胺五乙酸(gadolinium-diethylene triamine pentaacetic acid,Gd-DTPA)后,应用磁示踪法动态采集Gd-DTPA在脑间质系统(brain interstitial system, ISS)中的扩散和分布图像.利用自主研发的MRI影像测量分析系统软件对所获得的图像进行处理和分析,可获得各组大鼠脑尾状核区ECS内的有效扩散系数(DECS),清除率,容积占比和半衰期(T1/2)等参数.比较分析在不同给药速率下,老年大鼠与成年大鼠脑ECS内药物清除以及ECS结构功能的影响和差异.应用磁示踪DECS-mapping技术观察示踪剂在尾状核区的分布引流情况.结果: 0.1 μL/min注药速率下,与成年大鼠相比,老年大鼠的容积占比增加(18.20%±0.04% vs. 17.20%±0.03%,t=3.752,P=0.004),迂曲度下降(1.63±0.04 vs. 1.78±0.09, t=-3.680,P=0.004),药物清除速率下降[(1.94±0.68) mm 2/s vs. (3.25±0.43) mm 2/s,t=-3.971,P=0.003],ECS内分子扩散速率增快[(3.99±0.21)×10 -4mm 2/s vs. (3.36±0.37)×10 -4mm 2/s,t=3.663,P=0.004].注药速率增加到0.2 μL/min时,老年大鼠ECS内药物清除减慢[(2.53±0.45) mmol/L vs. (3.37±0.72) mmol/L,t=-1.828,P=0.021],但容积占比,ECS内分子扩散和宏观药物代谢参数无明显差异.注药速率增加到0.3 μL/min时,老年大鼠容积占比减小(17.20%±0.03% vs. 18.20%±0.05%,t=-0.869,P=0.045), ECS内药物清除明显加快[(4.04±0.76) mmol/L vs. (3.26±0.55) mmol/L,t=1.786,P=0.014],迂曲度和ECS内分子扩散速率无明显差异.结论: 老年脑CED给药在不同速率时ECS内药物清除及ECS结构参数发生改变,0.2 μL/min速率下CED给药对老年脑ECS影响最小.应用CED进行脑病治疗时应综合考虑年龄和注药速率等因素的影响,经ECS途径给药进行脑病微创治疗时应制定个体化临床治疗方案.
中图分类号:
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