双歧杆菌联合包裹液态氟碳阳离子脂质纳米粒增加HIFU消融效果:实验研究  

Bifidobacterium combined with cationic lipid nanoparticles with liquid perflurocarbon for improving HIFU ablation effect: Experimental study

作　　者：高悬 邹建中[1] 蒋冰蕾 徐蝶 罗勇 熊洁[1] 汪瑶台 唐瑜 郝兰[2] GAO Xuan;ZOU Jianzhong;JIANG Binglei;XU Die;LUO Yong;XIONG Jie;WANG Yaotai;TANG Yu;HAO Lan(College of Biomedical Engineering,Chongqing Medical University,State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology,Chongqing Key Laboratory of Biomedical Engineering,Chongqing Collaborative Innovation Center for Minimally-invasive and Noninvasive Medicine,Chongqing 400016,China;Institute of Ultrasound Imaging,Chongqing Medical University,Chongqing 400010)

机构地区：[1]重庆医科大学生物医学工程学院省部共建国家重点实验室培育基地-重庆市超声医学工程重点实验室重庆市生物医学工程学重点实验室重庆微无创医学协同创新中心,重庆400016 [2]重庆医科大学超声影像学研究所,重庆400010

出　　处：《中国介入影像与治疗学》2019年第5期309-314,共6页Chinese Journal of Interventional Imaging and Therapy

基　　金：重庆市科技计划项目(cstc2017jcyjAX0432)

摘　　要：目的探讨双歧杆菌联合包裹液态氟碳的阳离子脂质纳米粒对HIFU消融荷瘤鼠肿瘤组织的影响。方法培养双歧杆菌,并制备包裹液态氟碳的阳离子脂质纳米粒,检测体外连接率。建立人乳腺癌MDA-MB231细胞荷瘤鼠模型,将48只荷瘤鼠随机分为4组(每组12只),前后2次经尾静脉注射不同物质(间隔2天),其中A组(PBS组)2次均注射磷酸盐缓冲液(PBS),B组(双歧杆菌组)分别注射双歧杆菌、PBS,C组(阳离子脂质纳米粒组)分别注射PBS、阳离子脂质纳米粒,D组(双歧杆菌+阳离子脂质纳米粒组)分别注射双歧杆菌、阳离子脂质纳米粒。第2次注射完成后24 h,对荷瘤鼠肿瘤组织行HIFU辐照,分析肿瘤组织灰度变化。分别于HIFU辐照前1 h和辐照后1天行组织学检查,观察双歧杆菌的肿瘤靶向性,并测算肿瘤组织凝固性坏死体积和能效因子(EEF),行统计学分析,比较各组间的差异。结果双歧杆菌革兰染色呈蓝紫色的长棒状,表面电位-29 mV;阳离子脂质纳米粒呈球形,分布均匀,平均粒径(280.21±60.20)nm,表面电位25 mV。各组间灰度变化值(F=143.40)、凝固性坏死体积(F=243.20)、EEF(F=56.33)差异均有统计学意义(P均<0.001)。灰度变化值及凝固性坏死体积A组<B组<C组<D组,EEF:A组>B组>C组>D组,两两比较差异均有统计学意义(P均<0.05)。4组荷瘤鼠心、肝、脾、肺、肾组织及A、C组肿瘤组织中均无双歧杆菌生长;B、D组肿瘤组织中可见大量双歧杆菌。结论双歧杆菌联合包裹液态氟碳的阳离子脂质纳米粒可增强HIFU对荷瘤鼠肿瘤组织的消融效果。Objective To investigate the influence of bifidobacterium combined with cationic lipid nanoparticles with liquid fluorocarbon on HIFU ablation for tumor-bearing mice.Methods Bifidobacterium was cultured,cationic lipid nanoparticles with liquid fluorocarbon were prepared,and the connection ratio was examined in vitro.Mice models of human breast cancer MDA-MB231 cells were established.A total of 48 tumor-bearing mice were randomly divided into 4 groups (each n =12).Different substances were injected through the tail vein twice (two days apart).Tumor-bearing mice in group A (PBS group) were injected with phosphate buffer (PBS) twice,in group B (bifidobacterium group) were injected with bifidobacterium before PBS injection,in group C (cationic lipid nanoparticles) with PBS before cationic lipid nanoparticles injection and in group D (bifidobacterium+cationic lipid nanoparticle group) with bifidobacterium before cationic lipid nanoparticles injection.Twenty-four hours after the completion of the second injection,HIFU irradiation was performed on the tumor tissue of tumor-bearing mice,and the changes between pre- and post-ablation gray scale of the tumor tissue were analyzed.Histological examination was performed 1 h before HIFU irradiation and 1 day after irradiation,respectively.The tumor targeting of bifidobacterium was observed,and the coagulative necrotic volume of tumor tissues and energy efficiency factor (EEF) of HIFU ablation were measured.Statistical analysis was performed to compare the differences among 4 groups.Results Gram-stained bifidobacterium longum was manifested as blue-violet long rod with a surface potential of -29 mV.The cationic lipid nanoparticles were spherical and evenly distributed with average particle diameter of (280.21±60.20)nm and a surface potential of 25 mV.The differences of gray scale change ( F =143.40),coagulative necrotic volume ( F =243.20) and EEF ( F =56.33) were statistically significant among 4 groups (all P <0.001).Gray value change and coagulative necrotic volume graduall

关 键 词：二裂菌属 阳离子脂质纳米粒 高强度聚焦超声消融术 动物实验 

分 类 号：R-332[医药卫生] R445.1