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微泡造影剂介导的声空效应对胶质瘤大鼠血脑屏障通透性及替莫唑胺疗效的影响

发布时间:2019-05-19 14:44
【摘要】:目的观察微泡造影剂联合超声对胶质瘤大鼠血脑屏障通透性及化疗药物疗效的影响。方法通过透射电镜观察超微结构、Western blotting检测紧密连接蛋白claudin-5的表达、脑组织伊文蓝染色检测并确认影响Wistar大鼠血脑屏障通透性的最佳造影剂浓度及最佳超声模式。采用大鼠胶质瘤细胞系9L脑纹状体注射建立Wistar大鼠胶质瘤模型,予以替莫唑胺化疗(50mg/kg,连用5d)后,计算瘤体大小,ELISA检测血清中肿瘤标志物胶质纤维酸性蛋白(GFAP)的浓度。结果微泡造影剂联合超声可使血脑屏障内皮细胞间的连接松弛,最佳造影剂浓度为1ml/kg,最佳超声模式为间隙触发(间隙400ms)10min;声空效应组大鼠中伊文蓝通过血脑屏障的含量明显多于对照组(P0.05)。替莫唑胺化疗后,声空效应组肿瘤体积明显低于对照组,而血清GFAP浓度明显高于对照组(P0.05)。结论微泡造影剂联合超声可提高胶质瘤大鼠血脑屏障通透性及化疗药物的疗效。
[Abstract]:Objective to observe the effect of microbubble contrast agent combined with ultrasound on blood-brain barrier permeability and chemotherapeutic effect in glioma rats. Methods the expression of tight junction protein claudin-5 was detected by transmission electron microscope (, Western blotting), and the best contrast agent concentration and ultrasound mode affecting the permeability of blood-brain barrier in Wistar rats were detected by Yi Wen blue staining. The glioma model of Wistar rats was established by injection of rat glioma cell line 9L into striatum. The tumor size was calculated after treatment with temozolamine chemotherapy (50 mg 路kg ~ (- 1) for 5 days). The concentration of glial fibrillar acidic protein (GFAP), a tumor marker in serum, was detected by ELISA. Results the connection between endothelial cells of blood-brain barrier could be relaxed by microbubble contrast agent combined with ultrasound. The optimum concentration of contrast agent was 1 ml 路kg ~ (- 1), and the best ultrasound mode was gap trigger (gap 400ms) for 10 min. The content of Evans blue passing through the blood-brain barrier in the sound void effect group was significantly higher than that in the control group (P 0.05). After chemotherapy with temozolomide, the tumor volume in the acoustic void effect group was significantly lower than that in the control group, while the serum GFAP concentration was significantly higher than that in the control group (P 0.05). Conclusion Microbubble contrast agent combined with ultrasound can improve the permeability of blood-brain barrier and the curative effect of chemotherapeutic drugs in glioma rats.
【作者单位】: 重庆医科大学附属第一医院心内科;
【基金】:重庆市卫生局医学科研项目(2012-1-004)~~
【分类号】:R739.41

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