超声空化联合恩度抑制大鼠Walker-256肿瘤血管新生

目的 观察微泡增强超声空化毁损肿瘤微血管联合恩度对肿瘤血管新生的抑制作用。方法 对健康雄性SD大鼠40只于单侧大腿内侧皮下种植Walker-256肿瘤，随机均分为超声空化联合恩度组（A组）、恩度组（B组）、超声空化组（C组）和超声假照组（D组），每组10只，每天1次、连续给予相应干预3天；干预前、干预后1天和4天分别行二维超声及超声造影（CEUS）检查。之后获取肿瘤组织，行血管内皮生长因子A（VEGFA）免疫组织化学染色，测定微血管密度（MVD）。比较各组造影峰值强度（PI）、曲线下面积（AUC）、肿瘤体积及MVD。结果 干预后1天，CEUS中A组PI和AUC值明显低于其余各组（P均<0.05），B组和C组则低于D组（P均<0.05）；干预后4天，各组中A组PI和AUC值仍最低（P均<0.05），B组仍显著低于D组（P<0.05）。干预后1天，A组肿瘤体积（1.94±0.64）cm³最低，B组、C组均低于D组（P均<0.05）。干预后4天，A组肿瘤体积（5.25±1.74）cm³仍为各组中最低（P均<0.05）。各组MVD存在差异（F=30.121，P<0.001）。A组（18.33±3.10）、B组（24.17±2.16）MVD明显低于C组（30.43±4.17）和D组（31.57±1.74）（P均<0.05）。结论 微泡超声空化联合恩度治疗可显著减少肿瘤血流灌注，从而抑制大鼠Walker-256肿瘤新生血管生成及肿瘤生长。

Microbubbles enhanced ultrasound combining Endostar on angiogenesis of Walker-256 tumor in rats

Objective To investigate the effect of ultrasonic cavitation combining Endostar on angiogenesis of Walker-256 tumor. Methods Totally 40 healthy male SD rats with Walker-256 tumor implanted in unilateral hind limb were randomly divided into ultrasonic cavitation and Endostar group(group A), single Endostar group(group B), single ultrasonic cavitation group (group C) and sham cavitation group(group D). The interventions were given once a day for three consecutive days. Contrast-enhanced ultrasound (CEUS) was performed before and 1 day and 4 days after intervention, and peak intensity (PI) and area under curve (AUC) were recorded, while two-dimensional ultrasound was performed to measure the tumor volume. Four days after intervention, tumors were harvested for vascular endothelial growth factor A (VEGFA) immunohistochemical staining to analyze microvessel density (MVD). Results One day after intervention, significant differences of PI and AUC were found among group A and other three groups, also between group C and group D (all P<0.05). Four days after interventions, PI and AUC of group A were still lower than those of other groups (all P<0.05). One day after interventions, tumor volume was (1.94±0.64)cm³ in group A, lower than in other 3 groups, while in group B and C were lower than in group D (all P<0.05). Four days after interventions, the most retarded tumor growth was observed in group A (all P<0.05). Significant differences of MVD were found among groups (F=30.121, P<0.001), while MVD in group A and B were lower than in group C and D (both P<0.05). Conclusion Ultrasound cavitation combining with Endostar can disrupt tumor vasculature, inhibit angiogenesis and suppress tumor growth of Walker-256 tumor in rats.