微波消融联合载阿霉素微泡靶向击破在小鼠H22肝癌治疗中的效果观察  

Effect of microwave ablation combined with doxorubicin-loaded microbubbles targeted-destruction in treating experimental mice with H22 hepatocellular carcinoma

作　　者：范蕊 李田宽 王超[1] 董瑞 陈琪 郭金和[2] RAN Rui;LI Tiankuan;WANG Chao;DONG Rui;CHEN Qi;GUO Jinhe(School of Medicine,Southeast University,210009,China;Department of Interventional Radiology&Vascular Surgery,Zhongdn Hospital of Southeast University,Nanjing,Jiangsu Province 210009,China)

机构地区：[1]东南大学医学院,南京210009 [2]东南大学附属中大医院介入与血管外科

出　　处：《介入放射学杂志》2021年第3期258-263,共6页Journal of Interventional Radiology

基　　金：国家自然科学基金(81671795)。

摘　　要：目的观察微波消融(MWA)联合载阿霉素微泡靶向击破治疗小鼠H22肝癌皮下瘤的效果。方法制备空白微泡和载阿霉素微泡,检测其理化特性。流式细胞仪分析不同给药方式下体外细胞内药物浓度。构建BALB/c小鼠H22肝癌皮下瘤模型,将72只荷瘤小鼠随机均分为单纯MWA组(A组)、MWA+阿霉素组(B组)、MWA+空白微泡组(C组)、MWA+载阿霉素微泡组(D组),其中C、D组微泡经低频超声击破。记录小鼠肿瘤体积变化,构建Kaplan-Meier生存曲线,比较心、肾组织内药物浓度。病理切片检测各组残存活性肿瘤区微血管密度(MVD)和Ki-67表达,并进行统计学分析。结果体外细胞实验显示,低频超声靶向击破微泡技术能显著提高肿瘤细胞内药物浓度(P=0.011);体内实验显示,D组抑制肿瘤生长显著优于A组(P=0.0085),B组、D组小鼠生存时间均比A组显著延长(P=0.009,P=0.003),同时D组心、肾组织内药物浓度均显著降低(P=0.012,P=0.045)。D组残存活性肿瘤区MVD与A组相比显著降低(P<0.0001),B、D组肿瘤细胞Ki-67表达均显著降低(P<0.001)。结论MWA联合载阿霉素微泡超声靶向击破可提高肝癌细胞内药物浓度,抑制肿瘤增殖和微血管生成,弥补单纯MWA治疗适形性不足,同时降低药物心、肾不良反应。Objective To explore the effect of microwave ablation(MWA)combined with doxorubicin-loaded microbubbles targeted-destruction in the treatment of mouse H22 hepatocellular carcinoma.Methods Blank microbubbles and doxorubicin-loaded microbubbles were prepared and their physical and chemical properties were tested.Flow cytometry was used to analyze the concentration of drug in vitro.Subcutaneous H22 hepatocellular carcinoma tumor model was established in BALB/c mice.A total of 72 tumor-bearing mice were equally and randomly divided into four groups:MWA alone(group A,control group),MWA plus doxorubicin(group B),MWA plus blank microbubbles(group C),and MWA plus doxorubicinloaded microbubbles(group D).In group C and group D,the microbubbles were destructed by low-frequency ultrasound.The tumor growth curve was drawn and Kaplan-Meier survival curve was constructed.The drug concentrations in the heart and kidney tissues were compared.Micro-vessel density(MVD)and Ki-67 expressions in the residual active tumor areas were detected and statistically analyzed.Results Cellular experiments in vitro showed that low-frequency ultrasound targeted drug-loaded microbubbles destruction technique could remarkably increase the drug concentration in tumor cells(P=0.011).Experiments in vivo indicated that the inhibition degree of tumor growth in group D was significantly stronger than that in group A(P=0.0085).The survival time of mice in both group B and group D were obviously longer than that in group A(P=0.009 and P=0.003 respectively),meanwhile,the drug concentrations in heart and kidney tissues in group D were strikingly lower than those in group A(P=0.012 and P=0.045 respectively).Compared with group A,in group D the MVD in the residual active tumor areas was significantly lower(P<0.0001),and in both group B and group D the Ki-67 expressions in the residual active tumor areas were also remarkably decreased(P<0.001).Conclusion Microwave ablation combined with doxorubicin-loaded microbubbles targeted-destruction can significantly incr

关 键 词：微波消融 阿霉素 微泡 低频超声 肝癌 

分 类 号：R735.7[医药卫生—肿瘤]