相变高分子微球增效高强度聚焦超声消融裸鼠骨肉瘤

Application of phase-change type micropheres enhancing the efficacy of high intensity focused ultrasound ablating osteosarcoma in nude mice

目的制备相变高分子微球,观察其增效高强度聚焦超声(HIFU)消融裸鼠骨肉瘤模型的效果。方法制备包裹液态氟碳的高分子微球,检测其形态、结构、粒径电位及相变条件;建立裸鼠骨肉瘤模型,随机分为空白组(不予处理)、对照组(注射生理盐水)和实验组1、2、3(注射稀释倍数分别为5、10、20倍的Pct-MP溶液),处理后立即用海级星对肿瘤进行辐照。于辐照后即刻和72h提取标本并观察坏死面积、行HE染色,并对72h提取的标本的坏死周边组织进行细胞增殖和凋亡测定。结果成功制备相变高分子微球;HIFU辐照后即刻提取的标本,实验组1、2的坏死面积与对照组差异均有统计学意义(P均<0.05),但与实验组3的差异无统计学意义(P>0.05);72h后提取的标本,实验组1、2的坏死面积进一步扩大、与辐照后即刻提取的标本的差异有统计学意义(P均<0.05)。HIFU辐照72h后,实验组1、2、3与对照组间坏死周边组织的凋亡和增殖指数差异均有统计学意义(P均<0.05)。结论在骨肉瘤裸鼠模型中,自制相变高分子微球能够增强HIFU对于骨肉瘤的消融效果,增强作用与微球浓度有关。

Objective To prepare the phase-change type microspheres （Pct-MP） and observe the effect of high intensity focused ultrasound （HIFU） ablating xenograft tumor model of human osteosarcoma in nude mice. Methods Pct-MP was prepared and its form, particle size, surface potential and the condition of phase-change were detected. Xenograft tumor model of human osteosarcoma were established and randomly divided into blank group （without any intervention）, control group （treated with physiological saline） and experimental group 1, 2, 3 （treated with the Pct-MP emulsion diluted 5, 10 and 20 times respectively）, then each group was subjected to the HIFU ablation immediately. Specimens were taken to HE staining, necrosis area of osteosarcoma were calculated and compared immediately and 72 h after HIFU ablation. Prolifera- tion and apoptosis changes of the targeted region were analyzed 72 h after HIFU ablation. Results Pct-MP was prepared successfully. There were significant differences in the area of necrosis of osteosarcoma after the HIFU ablation between the control group and experimental group 1, 2 （both P^0.05）, but not with experimental group 3 （P〈0.05）. Experimental group 1 and experimental group 2 had a lager area of necrosis 72 h after HIFU ablation, compared to that after the HIFU ablation immediately （both P〈0.05）. There were significant differences in proliferation and apoptotic index of the target regions between the control group and all the experimental groups （all P〈0.05）. Conclusion In the xenograft osteosarco- ma model of nude mice, the Pct-MP can enhance the efficacy of HIFU ablating osteosarcoma, and the effects rely on the concentration of Pct-MP.