目的 探讨新型超声空化技术物理毁损肿瘤微血管的可行性并分析其病理机制.方法 将24只皮下荷Walker-256肿瘤的SD雄性大鼠随机分成3组,超声微泡组(n=8)、单纯超声组(n=8)、假照组(n=8).实验中,在静脉注射剂量为0.2 ml/kg的脂质微泡超声造影剂配合下,同时用新型超声空化治疗仪辐照肿瘤3 min;单纯超声组以等量生理盐水代替微泡;假照组注射微泡而超声假照.各组治疗前、治疗后0 min对肿瘤进行高分辨力超声造影检查和分析.最后,获取肿瘤标本进行病理检查.结果 超声微泡组治疗后,Walker-256肿瘤血流灌注完全消失,肿瘤造影平均灰阶值(GSV)由治疗前的121±12降为81±9(P<0.01);而假照组和单纯超声组治疗前后视觉血流灌注无明显变化,造影灰阶值分别为112±14和111±12,治疗后分别为(113±14) GSV和(103±13)GSV,两组治疗前后差异均无统计学意义(均P>0.05).微泡超声空化治疗后,肿瘤微血管扩张、管壁结构崩解,弥漫性出血和组织水肿和局部血肿血栓形成.结论 新型超声空化治疗技术能够毁损大鼠Walker-256肿瘤的微血管、阻断其微循环,可能成为一种新型的物理抗肿瘤血管生成方法.
Objective To explore the feasibility of disrupting tumor microcirculation by the cavitation of microbubbles enhanced ultrasound (US) and analyze its pathological mechanism.Methods Twenty-four SD male rats with subcutaneously transplanted Walker-256 tumor were divided into 3 groups,i.e.ultrasound plus microbubbles group (US + MB),US group and sham group.Pulsed US was delivered to tumor for 3 minutes during an intravenous infusion of microbubbles at 0.2 ml/kg in the US + MB group.The control groups received only the US exposure or the MB injection.Tumor perfusion was visualized with contrast enhanced ultrasound before and 0 ain after treatment.Finally the pathological examination was performed.Results The contrast perfusion of Walker-256 tumors vanished immediately after treatment in the US+ MB group and the gray scale value (GSV) decreased from 121 ±12 (pre-treatment) to 81 ±9 (posttreatment,P 〈0.01 ).There was no significant difference of GSV before and after treatment in two control groups (P 〉0.05).The GSV values were 112 ± 14 and 111 ± 12 pre-treatment and 113 ± 14 and 103 ± 13post-treatment in the sham and US groups.The pathological examination showed remarkable hemorrhage,endothelial injuries,increased intercellular edema and in situ thrombosis.Conclusion Microbubbleenhanced ultrasound can significantly disrupt tumor vasculature and block its circulation.And it may become a novel physical anti-angiogenetic therapy for tumor.