南方医科大学学报

南方医科大学学报 ›› 2019, Vol. 39 ›› Issue (09): 1009-.doi: 10.12122/j.issn.1673-4254.2019.09.02

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双歧杆菌改变肿瘤组织声学特性对高强度聚焦超声消融效果的影响

徐蝶，罗勇，高悬，熊洁，蒋冰蕾，汪瑶台，唐瑜，蒋富杰，王璐，李桦楠，乔海，邹建中   

  • 出版日期:2019-09-20 发布日期:2019-09-20

Effect of Bifidobacterium-induced changes in tumor tissue acoustic properties on efficacy of high-intensity focused ultrasound ablation

  • Online:2019-09-20 Published:2019-09-20

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摘要： 目的探讨双歧杆菌对裸鼠皮下肿瘤组织声学特性变化及高强度聚焦超声（HIFU）消融的影响。方法培养双歧杆菌，建立 人乳腺癌（MDA-MB-231）荷瘤鼠模型。将40只荷瘤裸鼠随机分为2组，即实验组（n=20）和对照组（n=20）。实验组连续3 d尾 静脉注射双歧杆菌悬液（200 μL、浓度4×108 cfu/mL），对照组连续3 d注射磷酸盐缓冲液（PBS，200 μL）。注射前、第1次注射后 第3天、第7天，采用剪切波弹性成像评估肿瘤组织硬度变化；注射后第7天（从第1次注射算起）两组均处死10只荷瘤鼠，剥离肿 瘤，插入式脉冲取代法测量肿瘤组织声速和声衰减；Masson染色观察肿瘤内胶原纤维改变、免疫组化行血小板-内皮细胞粘附分 子（PECAM-1/CD31）标记，评估组织内新生血管变化。两组各剩余的10只荷瘤鼠进行HIFU消融，通过对比辐照前/后灰度变 化值、凝固性坏死体积、能效因子和病理检查，评价消融效果。结果组织声学特性：实验组中胶原纤维形态粗大、排列致密，新 生血管含量较少呈条索状或点状；对照组肿瘤内胶原纤维形态细小、排列疏松，新生血管含量较多呈长条形或类圆形。双歧杆 菌定植于肿瘤内第7天，实验组肿瘤硬度大于对照组（P=0.01）。实验组超声波在肿瘤中的传播速度大于对照组（P=0.001）、声衰 减大于对照组（P=0.000）。HIFU消融效果：实验组灰度变化值平均值大于对照组（P=0.0006），凝固性坏死体积大于对照组（P= 0.0045），能效因子小于对照组（P=0.0134）。结论通过静脉注射双歧杆菌，可改变肿瘤组织胶原纤维含量、声传播速度、声衰减， 并减低HIFU辐照的能效因子，提高HIFU辐照效率。

Abstract: Objective To investigate the effects of Bifidobacterium on the acoustic characteristics of tumor tissue and how such acoustic changes affect the efficacy of high-intensity focused ultrasound (HIFU) ablation in nude mice. Methods Forty mice bearing human breast cancer cell (MDA-MB-231) xenograft were randomized into experimental group (n=20) and control group (n=20) for intravenous injection of Bifidobacterium suspension (200 μL, 4 × 108 cfu/mL) and PBS (200 μL) for 3 consecutive days, respectively. Before and at 3 and 7 days after the first injection, shear wave elastography was used to evaluate the hardness of the tumor tissue. On day 7 after the first injection, 10 mice from each group were sacrificed and the sound velocity and sound attenuation of the tumor tissues were measured. The changes in the collagen fibers in the tumors were evaluated using Masson staining, and neovascularization in the tumor was assessed with immunohistochemistry for platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). The remaining 10 tumor-bearing mice in each group were subjected to HIFU ablation, and the ablation efficiency was evaluated by assessing the changes in irradiation gray values, coagulative necrosis volume, energy efficiency factor (EEF) and irradiation area and by pathological examination with HE staining. Results In the experimental group, the collagen fibers in the tumor tissues were strong and densely aligned, and the tumors contained fewer new blood vessels showing strip-or spot-like morphologies. In the control group, the collagen fibers in the tumors were thin and loosely arranged, and the tumors showed abundant elongated or round new blood vessels. Bifidobacterium colonized in the tumor 7 days after the injection, and the tumor hardness was significantly greater in the experimental group than in the control group (P=0.01); the acoustic velocity (P=0.001) and the acoustic attenuation (P=0.000) of the tumor tissues were also greater in the experimental group. HIFU irradiation resulted in significantly greater changes in the gray scale of tumor (P=0.0006) and larger coagulative necrosis volume (P=0.0045) in the experimental group than in the control group, and the EEF was significantly smaller in the experimental group (P=0.0134). Conclusion Bifidobacterium can cause changes in collagen fiber content, acoustic velocity and attenuation in the tumor tissue and reduce the EEF of HIFU irradiation, thereby improving the efficacy of HIFU irradiation.