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微泡造影劑介導的聲空效應對膠質(zhì)瘤大鼠血腦屏障通透性及替莫唑胺療效的影響

發(fā)布時間:2019-05-19 14:44
【摘要】:目的觀察微泡造影劑聯(lián)合超聲對膠質(zhì)瘤大鼠血腦屏障通透性及化療藥物療效的影響。方法通過透射電鏡觀察超微結(jié)構(gòu)、Western blotting檢測緊密連接蛋白claudin-5的表達、腦組織伊文藍染色檢測并確認影響Wistar大鼠血腦屏障通透性的最佳造影劑濃度及最佳超聲模式。采用大鼠膠質(zhì)瘤細胞系9L腦紋狀體注射建立Wistar大鼠膠質(zhì)瘤模型,予以替莫唑胺化療(50mg/kg,連用5d)后,計算瘤體大小,ELISA檢測血清中腫瘤標志物膠質(zhì)纖維酸性蛋白(GFAP)的濃度。結(jié)果微泡造影劑聯(lián)合超聲可使血腦屏障內(nèi)皮細胞間的連接松弛,最佳造影劑濃度為1ml/kg,最佳超聲模式為間隙觸發(fā)(間隙400ms)10min;聲空效應組大鼠中伊文藍通過血腦屏障的含量明顯多于對照組(P0.05)。替莫唑胺化療后,聲空效應組腫瘤體積明顯低于對照組,而血清GFAP濃度明顯高于對照組(P0.05)。結(jié)論微泡造影劑聯(lián)合超聲可提高膠質(zhì)瘤大鼠血腦屏障通透性及化療藥物的療效。
[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.
【作者單位】: 重慶醫(yī)科大學附屬第一醫(yī)院心內(nèi)科;
【基金】:重慶市衛(wèi)生局醫(yī)學科研項目(2012-1-004)~~
【分類號】:R739.41

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