微泡双重击破效应对裸鼠HepG2肿瘤微血管的损伤作用

摘要

目的 研究微泡双重击破效应对裸鼠HepG2移植肿瘤微血管的损伤作用以及对血流灌注的阻断作用.方法 28只皮下荷人类肝癌HepG2肿瘤的裸鼠随机分为3组,超声微泡组经静脉推注脂质微泡0.1 ml并联合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,单纯微泡组推注微泡时进行超声假照.各组肿瘤治疗前后行超声造影检查,分析肿瘤造影的峰值强度及曲线下面积,最后获取肿瘤标本行光镜观察.结果 超声微泡组肿瘤造影的峰值强度百分比由(26.9±10.9)％下降至(8.2±5.8)％,曲线下面积由1210.4±823.1下降至291.6±255.2,差异有统计学意义(P＜0.05)；但两对照组肿瘤治疗前后造影峰值强度及曲线下面积变化均无显著差异.病理观察发现超声微泡组肿瘤血管内皮细胞肿胀、血管断裂,组织间隙内出血、水肿.结论 微泡双重击破效应可造成裸鼠HepG2肿瘤微血管物理损伤和血流灌注显著下降.%Objective To investigate the change of HepG2 liver tumor perfusion after microbubble enhanced ultrasound cavitation treatment and observe the related pathological injury.Methods Twenty eight Balb/c(nuu) nude mice transplanted subcutaneous HepG2 tumor were divided into three groups randomly,including the microbubble enhanced ultrasound cavitation group,the ultrasound group and the sham group.Microbubble enhanced ultrasound cavitation treatment was performed by 0.1 ml microbubbles intravenous injection combined with pulse ultrasound emission in experimental group,while in control groups only ultrasound exposure or microbubble injection were applied.The perfusion of tumors was imaged using contrast-enhanced ultrasonography before and after treatments.Time-intensity curve and peak intensity were analyzed.The tumors were then harvested for histological examination.Results The perfusion of HepG2 tumors almost vanished immediately after treatment in experimental group,with the peak intensity reduced from (26.9 ± 10.9)％ to(8.2 ± 5.8)％ (P ＜0.05).There was no significant changes before and after treatments (P ＞ 0.05) in the two control groups.Histological findings were disruption of the endothelia,significant hemorrhage and increased intercellular fluid.Conclusions Microbubble-enhanced ultrasound cavitation can significantly reduce tumor blood perfusion and disrupt tumor vascularture.This new ultrasound therapy can potentially become a new physical anti-angiogenetic therapy for liver tumor.