低频超声选择性开放血肿瘤屏障的实验性研究  

Low Frequency Ultrasound Selected for Evaluating Permeation of Blood-Tumor Barrier:Experimental Study in Rats

作　　者：张震[1] 夏春义[2] 刘云会[2] 薛一雪[3] 

机构地区：[1]中国医科大学附属第一医院急诊科,沈阳市110001 [2]中国医科大学附属盛京医院脑外科 [3]中国医科大学神经生物教研室

出　　处：《中国超声医学杂志》2008年第7期580-583,共4页Chinese Journal of Ultrasound in Medicine

基　　金：国家自然科学基金(No30400145;30570650;30600060);辽宁省自然科学基金(No20052102);教育部博士点学科专项基金(No20050159005)

摘　　要：目的探讨低频超声对血肿瘤屏障通透性的影响。方法试验用80只健康成年Wister大鼠。采用1MHz超声探头、功率12mW,对移植肿瘤部位照射时间为20s,按照射与否及照射后时间分为正常对照组、肿瘤对照组及实验组,测定血-肿瘤屏障通透性的改变,透射电镜观察微血管内皮细胞紧密连接及神经元超微结构改变。结果1MHz超声照射大鼠移植瘤部位后,血-肿瘤屏障通透性先增加后恢复至正常水平,即在3h达到峰值,12h恢复到照射前的水平。透射电镜超微结构显示超声照射后引起照射部位微血管内皮细胞的紧密连接开放;同时观察到照射后胶质瘤细胞呈现不同时期凋亡的改变,而正常神经元仅有膜结构的轻微改变。结论低频超声可以选择性、可逆性开放血肿瘤屏障,其机制可能与紧密连接的开放有关。Objective To investigate the effect of low frequecy ultrasound on the permeability of the bloodtumor barrier （BTB） in rats. Methods The neurogliocytoma rat model was treated locally with ultrasound at a frequency of 1 MHz and power of 12 mW for 20 s. Rats with tumor were divided into the control and test groups at different time points after the treatment, using normal rats as a blank control. The permeability of BTB was assessed by measuring the optical density of Evans blue in the tumor. Electron microscopy was used to visualise the opening of tight junctions in capillary endothelial cells and changes in the neuron ultrastructures. Results A biphasic change of BTB permeability in the ultrasound-treated brain with neurogliocvtoma was measured at different time points, showed an increase at first and then restored to the control level. The permeability was increased to its peak value at 3 h and restored to the control level at 12 h after treatment. By opening the inter-endothelial cell tight junctions in the tumors, the incease of the permeability in the BTB were observed through an electron microscope at 0. 5 h after treatment and closures of the tight junctions were seen at 12 h. Tumor cells showed different stages of apoptosis after ultrasound treatment. There was no considerable disruption present in the structure of treated normal neurons except a slight alteration in the cell membrane. Conclusions Low frequency ultrasound may selectively and reversibly increase the permeability of blood-tumor barrier, which may be related to opening inter-endothelial tight junctions.

关 键 词：低频超声 血肿瘤屏障 通透性 紧密连接 

分 类 号：R739.4[医药卫生—肿瘤]