高悬,邹建中,蒋冰蕾,徐蝶,罗勇,熊洁,汪瑶台,唐瑜,郝兰.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[J].中国介入影像与治疗学,2019,16(5):309-314
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
投稿时间:2019-01-28  修订日期:2019-04-08
DOI:10.13929/j.1672-8475.201901060
中文关键词:  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
英文关键词:bifidobacterium  cationic lipid nanoparticles  high-intensity focused ultrasound ablation  animal experimentation
基金项目:重庆市科技计划项目(cstc2017jcyjAX0432)。
作者单位E-mail
高悬 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  
邹建中 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 zoujzh@cqmu.edu.cn 
蒋冰蕾 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  
徐蝶 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  
罗勇 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  
熊洁 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  
汪瑶台 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  
唐瑜 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  
郝兰 重庆医科大学超声影像学研究所, 重庆 400010  
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中文摘要:
      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。
英文摘要:
      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 gradually increased in group A, B, C and D (pairwise comparison:All P < 0.05), while EEF trended from high to low in group A, B, C and D (pairwise comparison:All P < 0.05). There was no bifidobacterium in heart, liver, spleen, lung and kidney of tumor-bearing mice among 4 groups nor in tumors of group A and C. A quantity of bifidobacterium was found in tumor tissue of group B and D. Conclusion Bifidobacteriaum combined with cationic lipid nanoparticles with liquid fluorocarbon can enhance the ablation effect of HIFU ablation on tumor tissue in tumor-bearing mice.
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