对比观察脂质纳泡与微泡在高强度聚焦超声消融兔肝中的增效作用

Comparison of high intensity focused ultrasound synergistic effect of nanobubbles and microbubbles in rabbit liver

目的观察正常兔肝中脂质纳泡与微泡对高强度聚焦超声(HIFU)消融效果的影响,探讨纳泡的应用价值。方法采用机械振荡法联合低速离心制备纳泡,观察和分析纳泡及微泡的形态、大小及分布。18只健康新西兰兔随机分为3组:HIFU+生理盐水组、HIFU+微泡组及HIFU+纳泡组,耳缘静脉注入各溶液15s后开始HIFU辐照,辐照功率为180 W,辐照时间5s,观察HIFU辐照前后回声变化,检测靶区组织的凝固性坏死体积以及微细结构变化,并作统计学分析。结果制备的脂质纳泡粒径均一,纳泡、微泡的平均粒径分别为(588.00±53.02)nm、(3058.00±545.20)nm;HIFU+微泡组与HIFU+纳泡组,靶区凝固性坏死体积[(124.26±16.72)mm3,(121.35±11.25)mm3]差异无统计学意义(P>0.05),但均显著大于HIFU+生理盐水组(62.49±4.54)mm3(P均<0.05);各组坏死组织微细结构均严重破坏。结论脂质纳泡具有与微泡相同的HIFU增效作用,为纳泡在HIFU技术中的深入研究提供实验依据。

Objective To investigate the effect of high intensity focused ultrasound （HIFU） combined with nanobubbles or microbubbles on ablation of health rabbit liver and explore the practical application value of nanobubbles. Methods Nanobubbles were fabricated by mechanical oscillation and low speed centrifugation, and the appearance, particle size and distribution of nanobubbles and mierobubbles were observed and evaluated. Eighteen healthy New Zealand rabbits were randomly divided into three groups （HIFU ＋ normal saline group, HIFU ＋ microbubbles group, HIFU ＋ nanobubbles group）. Fifteen seconds before HIFU irradiation, normal saline solution and bubble agents was administrated intravenously by ear vein; the power of HIFU was 180 W, and the ablation time was 5 s. The echo changes of target tissue before and after HIFU ablation were observed. Coagulative necrosis volume of target tissue was measured, the fine structure of necrotic tissue was examined and statistical analysis was used. Results Nanobubbles were successfully prepared with uniform size, the mean diameters of nanobubbles and microbubhles were （588.00±53.02）nm and （3058.00± 545.20）nm respectively. The coagulative necrosis volume of target area was no statistical difference between HIFU＋microbubbles group （[124.26 ±16.72]mm^3） and HIFU＋nanobubbles group （[121.35±11.25] mm^3 ,P〉0.05）, but was obviously larger than that of HIFU＋normal saline group （[62.49±4.54]mm^3 , all P〈0.05）. The microstructure of necrotic tissue was not significantly different among three groups. Conclusion Nanobubbles were similar with microbubbles in efficient of HIFU therapy synergistic, which provides an experimental basis for the further study of nanobubbles in HIFU.