微泡增强的超声空化阻断肿瘤微循环的初步研究

目的研究微泡增强的超声空化阻断肿瘤微循环的可行性。方法 26只皮下VX_2肿瘤荷瘤兔随机分为超声微泡组、单纯超声组及假照组。超声微泡组经耳缘静脉推注微泡联合超声辐照肿瘤,单纯超声组以生理盐水代替微泡,假照组超声假照。各组治疗前、治疗后0、30和60min时间点对肿瘤进行超声造影,分析各时间点造影灌注峰值灰阶变化。结果超声微泡组肿瘤造影灰阶值(级)从治疗前的(67.8±13.3)级降至(29.7±20.1)级(P0.01),维持超过60min仍无明显再通;而单纯超声组、假照组肿瘤造影灰阶值无明显变化(P0.05)。结论微泡增强的超声空化能够有效阻断兔VX_2皮下肿瘤的微循环,其发生机制尚不清楚。     

微泡激励的超声空化阻断正常肝血流灌注的初步研究

目的探讨采用脉冲式超声激励微泡空化阻断兔正常肝脏血流的可行性及阻断的病理改变。方法健康新西兰大白兔24只随机分成3组,分别是超声微泡组、单纯超声组、假照组。经兔耳缘静脉注射脂质微泡,剂量0.1 ml/kg;同时超声治疗头垂直辐照兔肝脏300 s,超声能量以脉冲式发射,频率1.2 MHz,平均声强0.89 W/cm~2。靶区治疗前后进行超声造影检查和定量分析。最后,获取该区域肝组织标本,行病理学检查。结果超声微泡组治疗后肝组织血流灌注基本消失,而单纯超声组、假照组治疗前后无明显变化。超声微泡组治疗前后肝实质平均灰阶值(GSV)分别为115.27±3.8和1.16±0.7,治疗后肝实质GSV显著低于治疗前(P0.01),单纯超声及假照组治疗前后GSV无显著差别。病理检查,超声微泡治疗组肝组织出现大片充血、出血、血栓形成等。结论微泡增强的脉冲式超声空化可以造成正常肝的血流灌注暂时性阻断或者显著下降,阻断机制可能是肝实质出血、水肿和血栓形成。     

微泡激励的超声空化对兔前列腺的损伤作用

目的 探讨微泡激励的超声空化效应对正常兔前列腺组织的损伤作用.方法 30只新西兰雄性兔随机分为超声微泡组、单纯超声组和微泡假照组进行实验.超声微泡组经静脉推注微泡0.1 ml/kg,超声辐照10 min;单纯超声组超声辐照10 min;微泡假照组仅静脉推注微泡0.1 ml/kg.各组循环注射伊文思蓝(EB)溶液示踪.随后视觉观察和定量分析前列腺EB漏出量,并行光镜检查.结果 超声微泡组的前列腺EB漏出量明显大于微泡假照组、单纯超声组(P＜0.01);光镜观察超声微泡组前列腺微血管破裂,组织间隙大量出血,血肿形成.结论 微泡激励的超声空化对兔前列腺有明显的机械损伤作用.     

超声联合微泡阻断兔正常肝血流的再研究

目的 探讨采用改进声学参数的超声治疗仪激励循环微泡空化,延长正常兔肝血流阻断时间的可行性.方法 改进型脉冲式超声空化治疗仪,治疗头频率831 kHz,峰值负压4.3 MPa,平均声强1.25 W/cm2.9只新西兰大白兔麻醉后开腹暴露肝,经耳缘静脉缓慢推注微泡的同时予以超声辐照肝5min;其中6只分别于治疗前、治疗后即刻、30 min、60 min及48 h对治疗靶区行超声造影,视觉观察并用声学密度方法测量各时间点峰值强度(PI)变化;其余3只用于治疗后即刻病理学检查.结果 治疗前肝实质造影增强显著并且均匀,PI为(-51.88±4.26)dB,治疗后即刻靶区PI降至(- 62.53±4.83)dB,视觉观察血流灌注几乎完全消失,30～60 min后肝血流灌注呈缓慢恢复,48 h后几乎恢复正常,PI为(- 52.00±4.60)dB.治疗后即刻、30 min、60 min肝实质平均PI低于治疗前及治疗后48 h,差异均有统计学意义(P＜0.05),治疗前与治疗后48 h差异无统计学意义(P＞0.05).光镜下可见肝细胞弥漫性混浊肿胀,挤压肝窦及窦状间隙;门静脉周围出血、血肿形成.结论 超声联合微泡可以阻断正常兔肝的血流灌注达1h,其阻断机制可能主要是肝细胞肿胀.     

超声破坏靶向VEGFR2微泡治疗皮下结肠癌移植瘤的实验研究

目的 探讨靶向VEGFR2微泡结合超声辐照治疗结肠癌的效果.方法 将17只VEFGR2高表达的结肠癌皮下种植瘤Balb/C裸鼠模型分为三组:A组5只,为对照组,仅接受超声造影检查和假照;B组6只,空白脂质微泡结合超声辐照;C组6只,载靶向VEGFR2单抗的脂质微泡结合超声辐照,所有模型均用红色荧光蛋白标记.空化治疗前和空化后1周分别行超声造影和荧光摄片检查,测量肿块大小、荧光面积、荧光强度及血管密度,并进行比较.结果 治疗前裸鼠肿瘤长径、荧光面积、荧光强度及血管密度在各组间比较差异无统计学意义(P＞0.05);A组假照后肿瘤长径、荧光面积、荧光强度及血管密度均比假照前增加,差异有统计学意义(P＜0.05);B组辐照后荧光强度及血管密度均较空化前减小,差异有统计学意义(P＜0.05),而肿瘤长径和荧光面积差异不显著(P＞0.05);C组辐照后肿瘤长径、荧光面积、荧光强度及血管密度与辐照前比较均明显减小,差异有统计学意义(P＜0.01);治疗后A、B、C三组各参数两两比较差异有统计学意义(P＜0.05).结论 靶向VEGFR2脂质微泡能增强超声空化对结肠癌的治疗效果.     

微泡双重击破效应对裸鼠HepG2肿瘤微血管的损伤作用

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.     

不同占空比诊断超声联合微泡对乏血供肿瘤血流灌注的影响

目的 探讨不同占空比诊断超声联合微泡对大鼠乏血供肿瘤血流灌注的影响。 方法 选用wistar大鼠45只,于右侧背部皮下建立大鼠C6胶质细胞瘤模型,根据不同脉冲时间及间隔时间随机分为5组,每组9只：A组,脉冲时间5s,间隔时间1s;B组,脉冲时间1s,间隔时间1s;C组,脉冲时间1s,间隔时间5s;D组,脉冲时间5s,间隔时间5s;E组,超声假照。各组对应的治疗脉冲占空比分别为0.167%、0.1%、0.033%、0.1%和0。每组荷瘤大鼠经超声联合微泡治疗/超声假照10min,于治疗/假照前、治疗/假照后即刻分别行超声造影检查,获得时间-强度曲线(TIC),比较各组峰值强度(PI)、曲线下面积(AUC);对比分析各组肿瘤超声造影图像进行超声造影视觉评分;各组随机选取3只大鼠取肿瘤组织行HE染色,观察治疗/假照后病理学变化。 结果 与组内治疗前比较,A组、B组治疗后AUC值增加,差异有统计学意义(t=-2.726,-3.922;P=0.026,0.004),各组治疗/假照后PI值及C组、D组、E组AUC值与组内治疗/假照前比较差异无统计学意义(均P>0.05)。与C组、D组、E组比较,A组、B组超声造影视觉评分值较高,差异有统计学意义(均P<0.05),余组间无明显统计学差异(均P>0.05)。A组、B组可见较明显的血管扩张,A组部分血管周围组织内可见少量红细胞渗出,C组、D组、E组血管扩张不明显。 结论 脉冲时间5s,间隔时间1s,占空比0.167%及脉冲时间1s,间隔时间1s,占空比0.1%的低强度诊断超声联合微泡可增强乏血供肿瘤血流灌注,后者为相对安全的超声治疗声学参数。     

不同超声辐照时间空化作用对降低兔肝血流灌注效应影响的实验研究

目的探讨不同声空化辐照激励时间高声压超声空化作用对兔肝血流灌注降低的影响作用。方法选取健康新西兰大白兔27只,依据不同声空化辐照时间将其随机分为1 min空化组(T1组)、5 min空化组(T5组)及10 min空化组(T10组),每组各9只。所有动物均采用高峰值负压(P=2.0 MPa)超声脉冲联合经静脉脂质微泡注射进行肝脏超声空化辐照处理。于超声辐照前、辐照后即刻、辐照后30 min、辐照后60 min及辐照后24 h对各组均进行肝脏超声造影,比较辐照区域造影曲线下面积(AUC)及达峰时间(Tp)。辐照后24 h造影结束切取辐照区域肝脏组织,观察其病理改变情况。结果 T1、T5及T10组正常兔肝脏在高声压超声空化辐照后均出现血流灌注量下降和达峰时间延长,AUC分别由(4868.24±1098.47)%s、(4395.27±1784.42)%s、(5522.43±1444.29)%s降低至(1642.71±914.15)%s、(1825.51±874.96)%s、(1097.38±370.24)%s,Tp由(21.62±7.07)s、(22.67±5.21)s、(24.17±5.50)s增加至(42.23±19.12)s、(50.04±11.33)s、(51.98±12.06)s。随着时间延长各组AUC逐渐回升,Tp逐渐回落。重复测量结果显示,各造影参数组间效应及交互效应差异均无统计学意义(P_(组间)=0.171、0.432、0.724,P_(时间*组间)=0.905、0.472、0.230);组内效应差异均有统计学意义(均P0.01),其中T1组辐照后即刻及辐照后30 min AUC与辐照前比较差异均有统计学意义(均P0.05),T5组仅辐照后即刻AUC与辐照前比较差异有统计学意义(均P0.05),而T10组辐照后所有时间点AUC与辐照前比较差异均有统计学意义(P0.05);T1组辐照后即刻及辐照后60 min Tp与辐照前比较差异有统计学意义(P0.05),T5组辐照后即刻、60 min、24 h Tp与辐照前比较差异均有统计学意义(均P0.05),而T10组辐照后所有时间点Tp与辐照前比较差异均有统计学意义(均P0.05)。病理结果显示,三组肝脏组织均出现不同程度的肝脏细胞变性坏死,T10组目测坏死范围大于T5组及T1组。结论高声压超声空化作用可显著降低正常兔肝组织血流灌注量及灌注速率,但不同声空化辐照时间对其影响作用无显著差异。随着声空化时间的延长,组织血流灌注恢复减缓。     

超声空化阻断对兔肝血流灌注的影响

目的观察微泡增强的超声空化效应在阻断兔肝血流实验中可能造成的不良反应。方法将21只健康新西兰大白兔随机均分为单纯超声组、一次超声空化组和两次超声空化组。超声空化处理采用经静脉注射脂质微泡(剂量0.1ml/kg体质量)联合峰值负压4.3MPa的脉冲式超声直接照射开腹暴露的肝脏5min。对一次超声空化组仅治疗1次;两次超声空化组治疗1次后间隔1h后重复治疗;单纯超声组用3ml生理盐水替代微泡。在治疗前及治疗后即刻、30、60min及48h对各组肝脏实施CEUS,计算各时间点峰值强度(PI)变化。实验结束后每组取一只动物,获取肝脏标本,行病理检查。结果一次超声空化治疗后即刻、30 min,靶区肝实质由此前的均匀增强变为无增强,其PI值由(-51.88±4.26)dB降至(-62.53±4.83)dB;48h后血流灌注恢复,PI值升至(-52.02±4.59)dB。两次超声空化治疗后治疗后即刻、30min,非增强缺损面积大于一次超声组,PI值变化与一次治疗组类似。单纯超声组治疗前、后CEUS无明显变化。病理发现一次超声空化组及两次超声空化组肝脏出现散在微小坏死灶。结论微泡超声空化阻断肝血流后,血流灌注可在48h后自行恢复,肝脏坏死范围较小。     

超声造影评价载血管内皮细胞生长因子抑制剂微泡结合超声辐照对裸鼠皮下结肠癌移植瘤治疗效果的初步研究

目的 应用超声造影评价超声介导的载血管内皮细胞生长因子抑制剂(vascular endothelial growth factor inhibitor,VEGFI)微泡对实验裸鼠结肠癌的治疗效果.方法 18只皮下种植结肠癌肿瘤的Balb/c裸鼠模型随机分为三组:A组(6只)为对照组,接受裸脂质微泡超声造影检查及假照;B组(6只),裸脂质微泡超声造影检查及超声辐照;C组(6只),载VEGFI脂质微泡及超声辐照.辐照前、辐照后1d、辐照后1周分别进行实时超声造影检查,存储图像进行声学定量脱机分析,获取峰值强度(PI)、局部血容量(RBV)、局部血流量(RBF)等造影参数并加以比较.结果 辐照前三组PI、RBV、RBF差异无统计学意义(P＞0.05);A组假照后1 dPI、RBV、RBF高于假照前,但差异无统计学意义(P＞0.05),1周后PI、RBV、RBF明显高于假照前,差异有统计学意义(P＜0.05);B组辐照后1 dPI、RBF、RBV较辐照前减小,差异有统计学意义(P＜0.05),而1周后PI、RBF、RBV又上升,与辐照前比较差异无统计学意义(P＞0.05);C组辐照后1d、辐照后1周PI、RBV、RBF均较辐照前减小,差异有统计学意义(P＜0.05).结论 载VEGFI微泡联合超声辐照可以增强对实验裸鼠结肠癌的治疗效果.     

Ultrasound-Mediated Microbubble Cavitation Transiently Reverses Acute Hindlimb Tissue Ischemia through Augmentation of Microcirculation Perfusion via the eNOS/NO Pathway

Ultrasound-mediated microbubble cavitation improves perfusion in chronic limb and myocardial ischemia. The purpose of this study was to determine the effects of ultrasound-mediated microbubble cavitation in acute limb ischemia and investigate the mechanism of action. The animal with acute hindlimb ischemia was established using male Sprague-Dawley rats. The rats were randomly divided into three groups: intermittent high-mechanical-index ultrasound pulses combined with microbubbles (ultrasound [US] + MB group), US alone (US group) and MB alone (MB group). Both hindlimbs were treated for 10 min. Contrast ultrasound perfusion imaging of both hindlimbs was performed immediately and 5, 10, 15, 20 and 25 min after treatment. The role of the nitric oxide (NO) pathway in increasing blood flow in acutely ischemic tissue was evaluated by inhibiting endothelial nitric oxide synthase (eNOS) with N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME). In the US + MB group, microvascular blood volume and microvascular blood flow of the ischemic hindlimb were significantly increased after treatment (both p values <0.05), while the microvascular flux rate (β) increased, but not significantly (p > 0.05). The increases were observed immediately after treatment, and had dissipated by 25 min. Changes in the US and MB groups were minimal. Inhibitory studies indicated cavitation increased phospho-eNOS concentration in ischemic hindlimb muscle tissue, and the increase was significantly inhibited by L-NAME (p < 0.05). Ultrasound-mediated microbubble cavitation transiently increases local perfusion in acutely ischemic tissue, mainly by improving microcirculatory perfusion. The eNOS/NO signaling pathway appears to be an important mediator of the effect.     

超声击破微泡效应抑制兔VX_2肿瘤生长的实验研究

目的 探讨超声击破微泡效应抑制兔VX_2肿瘤生长的可行性.方法 21只移植有皮下VX_2肿瘤的新西兰大白兔,随机分为超声微泡治疗组、单纯超声组和假照组.经静脉注射脂质微泡的同时,脉冲式聚焦超声直接辐照肿瘤区域.单纯超声组和假照组分别用5 ml生理盐水和超声假照替代,每次10 min,每隔72 h治疗一次,采集各时间点肿瘤二维声像图和超声造影影像,测量肿瘤切面最大直径.结果 在30 d的实验周期内,微泡超声治疗组、单纯超声组和假照组的肿瘤平均直径分别从(1.1±0.1)cm、(1.2±0.1)cm、(1.2±0.1)cm生长至(2.1±0.5)cm、(3.0±0.9)cm、(3.4±0.7)cm,微泡超声治疗组肿瘤直径明显小于另两组.结论 超声击破微泡效应可阻断肿瘤微循环,有一定的抑制肿瘤生长作用.     

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

目的探讨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及其病理机制。方法将36只皮下VX2荷瘤兔随机平均分成3组:超声微泡组注入0.2ml/kg体质量微泡5ml,并辅以超声辐照10min;单纯超声组注入生理盐水5ml,辐照10min;单纯微泡组仅注入0.2ml/kg体质量微泡5ml,不进行超声辐照。CEUS观察各组治疗前、治疗后0、30min、60min时血流灌注情况,比较各时间点的灌注面积。治疗后即刻随机选取各组6只荷瘤兔处死,完整切取肿瘤,行病理学检查。结果超声微泡组治疗后即刻肿瘤血流灌注完全消失,灌注面积为0,但30min及60min后灌注有所恢复,各时间点治疗后灌注面积显著大于治疗前(均P<0.05);大体病理检查见肿瘤微血管扩张、管壁结构崩解,弥漫性充血、出血和肿瘤组织水肿,局部血肿,形成血栓等。单纯超声组及单纯微泡组治疗前、后造影剂灌注面积无差异,肿瘤内部未见出血、水肿等。结论低能量超声联合微泡能够阻断肿瘤微循环,可能是由于空化效应导致血管壁损伤,组织水肿对局部肿瘤血液循环产生阻力,从而阻断肿瘤血液循环。     

超声介导下携尿激酶靶向微泡在兔动脉内溶栓后的电镜观察

目的 探讨携尿激酶靶向微泡溶解兔动脉内血栓后下的形态学改变。方法 在24只新西兰大白兔单侧股动脉制作富含血小板的混合性血栓,分成4组,每组6只:①单纯超声照射组(US);②单纯尿激酶静脉注射组(UK);③超声照射+微泡造影剂+尿激酶静脉注射组(US+ M+ UK);④超声照射+RGDS微泡造影剂+尿激酶组(US+ R+ UK)。将RGDS、微泡造影剂(SonoVue)和尿激酶通过直接联合法配制成携尿激酶的靶向微泡,超声照射30 min,多普勒血流仪监测血流量变化评价溶栓效果,然后对其行HE染色、电镜检查。结果 US+ R+ UK组血流量完全恢复,实现完全再通（P＜0.001）,HE染色显示血栓完全溶解,扫描电镜检查示血栓的纤维网状结构破坏,透射电镜显示血栓的大量降解碎片。结论血栓纤维蛋白网状结构的破坏、纤维蛋白的溶解是携尿激酶靶向微泡在兔动脉内溶解血栓的主要电镜表现。     

尿激酶RGDS微泡在体溶栓的血流频谱特点与可能机制的实验研究

目的 用直接连接法制备的携尿激酶RGDS超声微泡溶解在体血栓,分析其血流频谱的特征性改变及可能的溶栓机制.方法 42只新西兰大白兔单侧股动脉制成富含血小板的混合性血栓模型,分成7组,每组6只:①单纯超声照射组(US);②超声照射+造影剂注射组(US+M);③单纯尿激酶静脉注射组(UK);④超声照射+微泡造影剂+尿激酶静脉注射组(US+M+UK);⑤超声照射+RGDS微泡造影剂组(US+R);⑥RGDS微泡造影剂+尿激酶静脉注射组(R+UK);⑦超声照射+RGDS微泡造影剂+尿激酶组(US+R+UK),进行在体溶栓治疗.将RGDS、微泡造影剂(SonoVue)和尿激酶通过直接联合法配制成6 ml的混悬液后经耳缘静脉注射,超声照射30 min,应用脉冲多普勒血流仪持续监测血流流速,对血流量和频谱变化特点进行分析.结果 120 min后US、UK、US+M、US+R及US+M+UK组血流量均未实现再通,R+UK组血流量实现部分再通,US+R+UK组血流量完全再通(P＜0.001).血流频谱特点为:未再通的各组在整个溶栓过程中血流频谱为持续小、低幅杂波;再通的R+UK组和US+R+UK组溶栓时血流频谱出现持续高幅、杂乱的波,US+R+UK组溶栓时超声波与血流频谱产生共振变化.结论 在体溶栓时通与不通的血流频谱各具特点,超声共振效应是促进溶栓的可能机制.     

Experimental research on therapeutic angiogenesis induced by hepatocyte growth factor directed by ultrasound-targeted microbubble destruction in rats.

OBJECTIVE: The purpose of this study was to explore the feasibility of therapeutic angiogenesis in myocardial infarction induced by hepatocyte growth factor (HGF) mediated by ultrasound-targeted microbubble destruction. METHODS: Forty Wistar rats were divided into 4 groups after the models of myocardial infarction were prepared: (1) HGF, ultrasound, and microbubbles (HGF+US/MB), (2) HGF and ultrasound, (3) HGF and microbubbles, and (4) surgery alone. Destruction of ultrasound-targeted microbubbles loaded with the HGF gene with an electrocardiographic trigger mode was performed in the HGF+US/MB group. All the rats were killed after being transfected for 14 days. Enhanced green fluorescent protein expression was examined in the myocardium, liver, and kidney in all groups by fluorescence microscopy; CD34 expression was detected by immunohistochemistry, and microvessel density (MVD) was counted in the high-power field on microscopy. Hepatocyte growth factor expression in the myocardium was detected by western blotting and an enzyme-linked immunosorbent assay. RESULTS: Enhanced green fluorescent protein expression was detected in the myocardium of the HGF+US/MB group, but a few areas of HGF expression were detected only in small vessels and the capillary endothelium, and no expression was found in the surgery-alone and HGF and microbubbles groups. The results of MVD counting by microscopy showed that the MVD in the myocardium of the HGF+US/MB group was the highest among all the groups. The results of western blotting and the enzyme-linked immunosorbent assay showed that the amount of HGF in the myocardium was highest in the HGF+US/MB group. CONCLUSIONS: Ultrasound-targeted microbubble destruction could deliver HGF into the infracted myocardium and produce an angiogenesis effect, which could provide a novel strategy for gene therapy of myocardial infarction.     

Characteristic Blood-Perfusion Reduction of Walker 256 Tumor Induced by Diagnostic Ultrasound and Microbubbles

Tumor angiogenesis is characterized by a defective, leaky and fragile microvascular construction, and microbubble-enhanced ultrasound (MEUS) with high-pressure amplitude is capable of disrupting tumor microvasculature and arresting blood perfusion. In this study, we tried to investigate whether the blood perfusion of a malignant tumor can be characteristically interrupted by combining microbubbles and diagnostic ultrasound (US). Twenty-nine Sprague-Dawley (SD) rats with subcutaneous Walker 256 tumors and seven healthy SD rats were included. Fifteen tumors were treated by MEUS, which combined constant microbubble injection and 20 episodes of irradiation by diagnostic US (i.e., acoustic radiation force impulse [ARFI] imaging). The other 14 tumors were treated by ARFI or sham US only. Seven skeleton muscles from healthy SD rats were also treated with MEUS, serving as the control. Contrast-enhanced ultrasound (CEUS) was performed before and after all treatments. The blood perfusion of the tumor MEUS group showed a significant drop immediately after treatment, followed by a quick, incomplete perfusion recovery within 10–20 min. The visual perfusion scoring result was consistent with the quantitative analysis by CEUS peak intensity. However, there were no significant perfusion changes in the tumor control groups or the muscle control group. Histologic examination found severe microvascular disruption and hemorrhage in the MEUS-treated tumors but not in the control groups. Therefore, the treatment combining diagnostic US and microbubbles can specifically decrease or interrupt the blood perfusion of Walker 256 tumors, which could be a potential new imaging method for diagnosing malignant tumors.     

Antitumor Effect of Docetaxel‐Loaded Lipid Microbubbles Combined With Ultrasound‐Targeted Microbubble Activation on VX2 Rabbit Liver Tumors

Objective. The purpose of the study was to explore the antitumor effect of docetaxel‐loaded lipid microbubbles combined with ultrasound‐targeted microbubble activation (UTMA) on VX2 rabbit liver tumors. Methods. Docetaxel‐loaded lipid microbubbles were made by a mechanical vibration technique. VX2 liver tumor models were established in 90 rabbits, which were randomly divided into 6 groups, including control, docetaxal‐loaded lipid microbubbles alone, docetaxal alone, docetaxal combined with ultrasound, pure lipid microbubbles combined with ultrasound, and docetaxel‐loaded lipid microbubbles combined with ultrasound (DOC+MB/US). The tumor volume and inhibition rate (IR) of tumor growth were calculated and compared. Apoptosis was detected by terminal deoxyuridine nick end labeling. Proliferating cell nuclear antigen and matrix metalloproteinase 2 (MMP2) protein expression was detected by immunohistochemistry. Caspase 3 and MMP2 messenger RNA (mRNA) expression was detected by in situ hybridization histochemistry. The tumor metastasis rate and survival time of the animals were compared. Results. The IR and apoptotic index of the DOC+MB/US group were the highest among all groups, and the proliferating labeling index was the lowest. Matrix metalloproteinase 2 protein and mRNA expression in the DOC+MB/US group was the lowest among all groups, and caspase 3 mRNA expression in the DOC+MB/US group was the highest. The extensive metastasis rate in the DOC+MB/US group was the lowest, and the survival time of the animals in the DOC+MB/US group was the longest. Conclusions. Docetaxel‐loaded lipid microbubbles combined with UTMA could inhibit the growth of VX2 rabbit liver tumors by deferring proliferation and promoting apoptosis, which may provide a novel targeted strategy for chemotherapy of liver carcinoma.