超声联合微泡影响肿瘤组织间质液压并增加化疗药物的转运的研究  

Ultrasound Combined with Microbubbles Increase the Delivery of Doxorubicin by Reducing the Interstitial Fluid Pressure

作　　者：肖妮娜 柳建华 金文慧 Xiao Nina;Liu Jianhua;Jin Wenhui(Department of Ultrasound,Guangzhou First People's Hospital,The Second Affiliated Hospital of South China University of Technology,Guangzhou.Guangdong 510180,China)

机构地区：[1]华南理工大学附属第二医院广州市第一人民医院超声医学科,广州市510180

出　　处：《中国超声医学杂志》2021年第12期1416-1419,共4页Chinese Journal of Ultrasound in Medicine

摘　　要：目的研究超声联合微泡是否可以有效降低肿瘤组织内的间质液压并增加盐酸阿霉素的渗透。方法本研究选取48只新西兰荷瘤兔并随机分为6组,即超声微泡阿霉素组(Ad-US-MB)8只、超声微泡组(US-MB)8只、超声组(US)8只、微泡组(MB)8只、阿霉素组(Ad)8只及对照组(BC)8只。予实验组缓慢静脉注射盐酸阿霉素化疗后,即刻予超声微泡治疗10 min。对各组干预前后,均采用wick-in-needle方法来测定荷瘤兔的肿瘤内间质液压(IFP),检测盐酸阿霉素的浓度,并观察肿瘤组织内盐酸阿霉素空间分布及肿瘤微血管形态。结果在实验干预后,Ad-US-MB组和US-MB组的IFP较实验干预前明显降低(P=0.01、0.013),Ad-US-MB组的盐酸阿霉素浓度(0.682±0.0001)较Ad组(0.422±0.357)的盐酸阿霉素浓度增加(P<0.05)。Ad-US-MB组与Ad组相比,肿瘤微血管周围有高密度的阿霉素分布。结论超声联合微泡可以影响肿瘤组织的间质液压,并提高盐酸阿霉素的转运效率。Objective To determine the change interstitial fluid pressure(IFP) after the therapy of pulsed low frequency ultrasound combined the microbubbles and the change of the doxorubicin penetration in VX2 tumor. Methods In this study, all of the 48 tumor-bearing rabbits were divided into 6 groups randomly(n=8 per group). These 6 groups contains doxorubicin therapy together with ultrasound(US) combined with microbubble(MB) treatment group(Ad-US-MB treatment group), US-MB treatment group, US treatment group, MB treatment group, Doxorubicin treatment group(Ad treatment group) and controlled group. The animals were intravenous injected with doxorubicin hydrochloride, and then the tumor of the animals were disposed by low-intensity ultrasound and mirobubbles for 10 minutes. The interstitial fluid pressure(IFP) of tumor tissues in rabbits were detected before and after intervention. Rabbits in each group were sacrificed immediately after treatment. The concentration and the distribution of doxorubicin were detected. Results The tumor IFP was significantly lower than pre-treatment in Ad-US-MB treatment groups and US-MB treatment groups(P=0.01, 0.013). Ultrasound combined with microbubble increased the concentration of doxorubicin in sample of Ad-US-MB treatment groups, compare to Ad treatment groups(P<0.05). In immunofluorescent staining section, high concentrations of doxorubicin were observed mainly around bloodvessels, and some even discovered at farther area in Ad-US-MB treatment groups. Conclusions The pulsed low frequency ultrasound combined the microbubbles enhance the vascular clearance of particles into the tumor interstitium by reducing IFP.

关 键 词：肿瘤间质液压 超声 微泡 阿霉素 肿瘤微血管 

分 类 号：R445.1[医药卫生—影像医学与核医学] R730.53[医药卫生—诊断学]