杨钰楠,高云华,谭开彬,刘平,付赤学.诊断超声联合微泡促顺铂跨血脑屏障转运的实验研究[J].中国医学影像技术,2009,25(6):938~941 |
诊断超声联合微泡促顺铂跨血脑屏障转运的实验研究 |
Blood brain barrier permeability of Cisplatin increase induced by transcranial ultrasound and microbubbles in an in vitro model |
投稿时间:2008-10-27 修订日期:2008-11-25 |
DOI: |
中文关键词: 血脑屏障 超声检查 微泡 顺铂 |
英文关键词:Blood brain barrier Ultrasonography Microbubble Cisplatin |
基金项目:国家自然科学基金(30670545)。 |
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中文摘要: |
目的 探讨诊断超声联合超声造影剂(微泡)促顺铂跨体外血脑屏障(BBB)模型的可行性。方法 利用BALB/c小鼠脑微血管内皮细胞(BMVEC)建立BBB体外实验模型,根据是否加入微泡和超声辐照,分为四组:对照组、超声组、微泡组和超声联合微泡组。每组添加浓度为5 ng/μl的生物素胶体金50 μl和顺铂,顺铂达到9 μg/cm2,供池定容在460 μl,分别于超声辐照后再培养48 h,并在培养不同时间点从受池中取样,通过高效液相色谱法(HPLC)检测顺铂的通透率;透射电镜观察细胞膜与细胞内超微结构的变化以及胶体金的分布;实验前后细胞小室行扫描电镜能谱分析。结果 2 MHz、0.6 W/cm2、10 min的诊断超声辐照联合脂膜微泡(1 μl/ml)能够促顺铂跨体外BBB模型的转运,透射电镜观察到内皮细胞胞饮小体增多,细胞内可见胶体金分布;单纯超声辐照组细胞间隙可见少量胶体金分布,对照组和微泡组细胞内外均不能见到胶体金;扫描电镜能谱分析,各组碳和锌元素总量均无改变,而超声组和超声联合微泡组两种元素的能谱分布发生转变。经HPLC检测,顺铂通透量超声组与超声联合微泡组显著高于对照组与微泡组,组间比较差异有统计学意义。结论 微泡联合诊断超声波能通过短暂开放紧密连接,促进药物顺铂跨BBB的转运。 |
英文摘要: |
Objective To investigate the feasibility of transcranial ultrasound and microbubbles to increase blood brain barrier permeability to Cisplatin in an in vitro model. Methods Twenty-four transwells were divided into ultrasound combined microbubbles (UCM) group, ultrasound group, microubbbles group and control group randomly, all were added 50 μl colloidal gold (5 ng/μl) and 9 μg/cm2 Cisplatin. The Cisplatin permeability was detected with HPLC technique. The ultrastructure of brain microvascular endothelial cells (BMVEC) and colloidal gold distribution were observed under transmission electron microscope. Spectrum analysis was used to detect the two important trace elements of Carbon and Zinc on the BBB. Results UCM and ultrasound sonicated by transcranial Doppler with 2 MHz, 0.6 W/cm2 and 10 min exposure. The ultrastructure of BMVEC in group UCM changed greatly from pinocytosis to Colloidal gold distribution in the cells. Minor Colloidal gold existed between the cells in group ultrasound, neither in the control nor microbbles group. Spectrum analysis indicated that the UCM and ultrasound affected the spectrum distribution of this trace element Carbon and Zinc. BBB permeability of Cisplatin increased greatly in the UCM and ultrasound group. Conclusion Transcranial ultrasound associated with MBs effectively increases the permeability of Cisplatin on the BBB in vitro, which may open the BBB reversibility. |
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