微泡诱导超声空化联合血凝酶对兔VX2肝癌微血管阻断作用的实验研究
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摘要
目的探讨微泡诱导超声空化联合血凝酶对兔VX2肝癌微血管损毁及阻断的作用。方法 32只VX2荷瘤兔随机分为4组:生理盐水组、血凝酶组、空化组和联合组,每组均为8只。4组均经相应的空化假辐照或空化治疗,于实验前后分别行超声造影检查,使用定量图像分析软件分析实验前后CEUS的峰值灰阶值(Peak)变化,通过光镜(HE)观察及透射电镜超微结构显示比较4组的治疗效果。结果实验前后,生理盐水组和血凝酶组超声造影图像视觉分析及定量分析Peak值比较均无明显变化(P>0.05)。空化组和联合组视觉观察可见造影灌注缺损,联合组缺损更为明显。HE染色显示:空化组内偶见局灶片状出血;联合组可见大片状出血及明显的细胞水肿。透射电镜显示:空化组和联合组的微血管壁破坏,基底膜不完整。结论微泡诱导超声空化联合血凝酶能促进内皮损伤并导致更广泛的血栓形成,同时验证了血凝酶可选择性针对肿瘤组织局部损伤的血管,引起快速血栓形成及血流阻塞,并有增强热消融的作用。
Objective To investigate the effects and mechanisms of microbubble-enhanced ultrasound combined with prothrombin on blocking and damaging regional circulation in rabbit VX2 liver tumors.Methods 32 animals with VX2 tumors were randomly divided into four groups.They were 8 with the physiological saline group,8 with the prothrombin group,8 treated with cavitation group and 8 with combined group.Corresponding treatment were used in 4 groups:Contrast-enhanced ultrasound was performed on the exposed liver tumors before and after treatment,and acoustic quantification was done and Peak value was obtained to assess the perfusion of liver tumors.Then,the liver tumors were harvested and examined under light microscopy with HE stain and transmission electron microscopy to compare the effects of treatment among all groups.Results CEUS images and peak values of the physiological saline group and the prothrombin group showed no statistical significance(P>0.05).Both of cavitation group and combined group showed defects in the contrast filtration,but it was more obvious in combined group.Piecemeal hemorrhage and intercellular edema were occasionally found in cavitation group under light microscopy.Obvious cellular edema and hematoma were observed in combined group.Transmission electron microscopy showed that microvascular walls were disrupted and the basement membranes were incomplete in cavitation group and combined group.Conclusions Microbubble-enhanced ultrasound combined with prothrombin promotes the endothelial damage and produces larger thrombotic area in liver tumor.It is also verified that prothrombin can selectively cause the injured microvascular of liver tumor to form thrombus and block blood flow quickly,and it enhanced thermal ablation effects.
Objective To investigate the effects and mechanisms of microbubble-enhanced ultrasound combined with prothrombin on blocking and damaging regional circulation in rabbit VX2 liver tumors.Methods 32 animals with VX2 tumors were randomly divided into four groups.They were 8 with the physiological saline group,8 with the prothrombin group,8 treated with cavitation group and 8 with combined group.Corresponding treatment were used in 4 groups:Contrast-enhanced ultrasound was performed on the exposed liver tumors before and after treatment,and acoustic quantification was done and Peak value was obtained to assess the perfusion of liver tumors.Then,the liver tumors were harvested and examined under light microscopy with HE stain and transmission electron microscopy to compare the effects of treatment among all groups.Results CEUS images and peak values of the physiological saline group and the prothrombin group showed no statistical significance(P>0.05).Both of cavitation group and combined group showed defects in the contrast filtration,but it was more obvious in combined group.Piecemeal hemorrhage and intercellular edema were occasionally found in cavitation group under light microscopy.Obvious cellular edema and hematoma were observed in combined group.Transmission electron microscopy showed that microvascular walls were disrupted and the basement membranes were incomplete in cavitation group and combined group.Conclusions Microbubble-enhanced ultrasound combined with prothrombin promotes the endothelial damage and produces larger thrombotic area in liver tumor.It is also verified that prothrombin can selectively cause the injured microvascular of liver tumor to form thrombus and block blood flow quickly,and it enhanced thermal ablation effects.
引文
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[3]朱梅,李佩倞,钟渝,等.低能量脉冲式超声联合微泡对兔VX2肿瘤微循环的阻断作用[J].中国医学影像技术,2012,28(4):621-625.
[4]钟渝,刘政,朱梅,等.新型超声空化技术毁损大鼠Walker-256肿瘤微血管的研究[J].中华医学杂志,2012,92(7):487-491.
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[6]皋月娟,刘政,赵宝珍,等.微泡激励的超声空化阻断正常肝血流灌注的初步研究[J].中国超声医学杂志,2010,26(2):104-107.
[7]刘昕悦,杨倩,高琴琴,等.微泡增强超声空化联合血凝酶对兔肝局部微血管阻断作用的实验研究[J].中国超声医学杂志,2015,31(4):369-372.
[8]石颖,谷芬,朱燕妮,等.微泡诱导超声空化联合血凝酶增强兔肝脏微波热消融作用的实验研究[J].中国超声医学杂志,2017,33(6):561-564.
[9] WOOD A K,BUNTE R M,COHEN J D,et al.The antivascular action of physiotherapy ultrasound on a murine tumor:role of a microbubble contrast agent[J].Ultrasound Med Biol,2007,33:1901-1910.
[2]赵洋,高顺记,刘政,等.超声击破微泡效应抑制兔VX2肿瘤生长的实验研究[J].中华超声影像学杂志,2010,19(4):352-355.
[3]朱梅,李佩倞,钟渝,等.低能量脉冲式超声联合微泡对兔VX2肿瘤微循环的阻断作用[J].中国医学影像技术,2012,28(4):621-625.
[4]钟渝,刘政,朱梅,等.新型超声空化技术毁损大鼠Walker-256肿瘤微血管的研究[J].中华医学杂志,2012,92(7):487-491.
[5] OHL C D,ARORA M,IKINK R,et al.Sonoporation from jetting cavitation bubbles[J].Biophys J,2006,91:4285-4295.
[6]皋月娟,刘政,赵宝珍,等.微泡激励的超声空化阻断正常肝血流灌注的初步研究[J].中国超声医学杂志,2010,26(2):104-107.
[7]刘昕悦,杨倩,高琴琴,等.微泡增强超声空化联合血凝酶对兔肝局部微血管阻断作用的实验研究[J].中国超声医学杂志,2015,31(4):369-372.
[8]石颖,谷芬,朱燕妮,等.微泡诱导超声空化联合血凝酶增强兔肝脏微波热消融作用的实验研究[J].中国超声医学杂志,2017,33(6):561-564.
[9] WOOD A K,BUNTE R M,COHEN J D,et al.The antivascular action of physiotherapy ultrasound on a murine tumor:role of a microbubble contrast agent[J].Ultrasound Med Biol,2007,33:1901-1910.