微泡诱导超声空化联合凝血酶增强的微波热消融治疗兔VX2肝癌的转归及生物学效应  

The outcomes and bioactivities of microbubble-enhanced ultrasound combined with prothrombin on microwave ablation in rabbit VX2liver tumors

作　　者：石颖[1] 张俊旺[2] 谷芬 贺建国 周晓东 Shi Ying;Zhang Junwang;Gu Fen;He Jianguo;Zhou Xiaodong(Department of Ultrasound,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第二医院超声诊断科,太原030001 [2]山西医科大学第二医院消化科,太原030001 [3]空军军医大学(第四军医大学)西京医院超声科

出　　处：《中华超声影像学杂志》2018年第11期1000-1004,共5页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金面上项目(81371567);山西医科大学博士启动基金(BS201716).

摘　　要：目的通过超声造影、组织病理学和透射电镜等方法,探讨微泡诱导超声空化联合凝血酶增强微波热消融技术治疗兔VX2肝癌的连续性生物效应及转归。方法80只VX2肝癌新西兰大白兔随机分为4组(每组20只):生理盐水组、凝血酶组、空化组和联合组。四组均经相应的空化假辐照或空化治疗,空化治疗后行微波热消融,于消融后0、3、7、14d4个时间点每组随机选取5只动物行超声造影测量消融区体积。对消融区、过渡区和周围区组织行组织病理学观察及透射电镜显示组织细胞超微结构,并通过视觉观察对肿瘤转移进行分级。结果消融后0、3、7、14d联合组消融区体积明显大于其他三组(均P<0.001)。消融后7、14d,HE染色显示联合组纤维包裹带厚度明显大于其他三组(均P<0.05)。透射电镜显示,消融后0d,联合组消融区内组织细胞结构较其他三组破坏严重;消融后7d,联合组过渡区细胞内线粒体损伤更严重。消融后7d和14d,联合组相比其他三组肿瘤转移程度轻,转移时间晚。结论微泡诱导超声空化联合凝血酶可增加兔VX2肝癌微波热消融的体积,增强组织细胞的破坏,抑制肿瘤的转移。同时,过渡区纤维包裹带形成可促进消融区周边组织的机化和修复。Objective To investigate the sequential biological effects and outcomes of microbubbleenhanced ultrasound (MEUS)combined with prothrombin on microwave ablation (MWA)in rabbit VX2 liver tumors using examination of transmission electron microscopy,histopathology and contrast-enhanced ultrasound(CEUS).Methods Eighty New Zealand rabbits with VX2 liver tumors were randomly divided into 4 groups (20 per group),including physiological saline group,prothrombin group,cavitation of microbubbles group (cavitation group)and cavitation of microbubbles combined prothrombin group (combined group).After treatment,the targeted liver tumors in all groups were ablated with MWA.On the 0,3,7 and 14d,the volumes of coagulated areas of 5 rabbits of each group randomly were measured using CEUS.Tissues in ablated areas,transition areas and surrounding areas were examined under light microscopy with histopathology and transmission electron microscopy to observe the differences among 4 groups.Tumor metastasis was graded using visual method.Results On the 0,3,7 and 14d,the coagulated volumes in combined group were larger than those in remaining 3 groups (all P<0.001).Under light microscopy with HE stain,in transition area,the fibra band in combined group was wider than those in remaining 3 groups on the 7 and 14 d (all P<0.05).The observations under transmission electron microscopy showed that the cellular ultrastructure disorder in ablated area on the 0 d and mitochondrial injury in transition area on the 7 d were more severe in combined group than those in remaining 3 groups. Compared with the remaining 3 groups,the degree of tumor metastasis in combined group was less,and the time of ocurrence was later.Conclusions MEUS combined with prothrombin can significantly expand ablation volume,enhance the necrosis of ablated tissues,and inhibit tumor metastasis on rabbit VX2 liver tumors.The fibra bands in the transition areas can promote the organization and repair the surrounding tissue in the ablation areas.

关 键 词：超声空化 微波消融 凝血酶 VX2肝癌 

分 类 号：R445.1[医药卫生—影像医学与核医学] R735.7[医药卫生—诊断学]