| 冯爽,乔伟,益磋,朱琼,李佩倞,刘政.不同机械指数诊断超声联合微泡对裸鼠胰腺癌移植瘤化疗的影响[J].中国介入影像与治疗学,2019,16(2):107-111 |
| 不同机械指数诊断超声联合微泡对裸鼠胰腺癌移植瘤化疗的影响 |
| Impact of diagnostic ultrasound with different mechanical index enhanced by microbubbles on chemotherapy of nude mice bearing pancreatic tumor |
| 投稿时间：2018-09-29 修订日期：2018-12-28 |
| DOI：10.13929/j.1672-8475.201809054 |
| 中文关键词: 胰腺肿瘤 药物治疗 超声检查 微泡 小鼠 模型,动物 |
| 英文关键词:pancreatic neoplasms drug therapy ultrasonography microbubbles mice models,animal |
| 基金项目:国家重点研发计划数字诊疗装备研发重点专项（2017YFC0107300）。 |
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| 中文摘要: |
| 目的 探讨不同机械指数（MI）诊断超声联合微泡对裸鼠人胰腺癌荷瘤模型肿瘤局部血流及化疗药物浓度的影响。方法 经裸鼠双侧后腿注射肿瘤细胞，建立裸鼠人胰腺癌荷瘤模型33只，随机分为A、B、C组，行超声造影、化疗药物注射及超声辐照/假照。随机选取荷瘤裸鼠一侧后腿为治疗侧（超声辐照），另一侧为对照侧（超声假照）。辐照/假照前后均行超声造影，获得时间-强度曲线，峰值强度（PI）及AUC。于超声辐照/假照前经尾静脉注射阿霉素（DOX），并于超声辐照/假照过程中实时推注微泡；A、B、C组治疗侧超声辐照的MI分别为0.3、0.7、1.1。超声辐照/假照后，行DOX药物浓度检测及组织病理检查。并于超声辐照/假照前，测定不同MI对应的峰值负压范围。结果 A组治疗侧DOX药物浓度明显高于对照侧[（1.45±0.53）μg/g vs（1.07±0.46）μg/g；t=-5.163，P=0.001]。B组及C组中，治疗侧与对照侧药物浓度差异均无统计学意义（Z=-0.297、-0.357，P=0.766、0.721）。超声造影定量分析显示，除B组对照侧PI、B组及C组对照侧AUC外，超声辐照/假照后各组中治疗侧及对照侧均较超声辐照/假照前PI均升高、AUC均增大（P均<0.05）。各组对照侧与治疗侧肿瘤组织病理表现相似，未见明显出血及细胞肿胀。MI为0.3（A组）、0.7（B组）、1.1（C组）时，对应的实测峰值负压范围分别为0.81~0.83 MPa、0.96~1.32 MPa和2.29~2.53 MPa。结论 MI为0.3的诊断超声联合微泡可增强肿瘤局部血流灌注，促进人胰腺癌荷瘤裸鼠肿瘤局部化疗药物释放。 |
| 英文摘要: |
| Objective To investigate the impact of diagnostic ultrasound (DUS) with different mechanical index (MI) combined with microbubbles on tumor blood flow and chemotherapeutic drug concentration in nude mice bearing human pancreatic cancer. Methods Pancreatic tumor models were established through injecting tumor cell suspension into bilateral hind limbs in 33 nude mice,which were divided into three groups (group A, B and C) randomly. Contrast-enhanced ultrasound (CEUS), chemotherapeutic agents injection and exposure/sham exposure with DUS were performed on all models in the three groups. For each model, one of the hind limb was chosen as therapeutic side (exposure), and the other hind limb as control side (sham exposure). CEUS was performed before and after ultrasonic exposure/sham to obtain the time-intensity curve (TIC), peak intensity (PI) and AUC. Doxorubicin was injected through the tail vein before ultrasonic exposure/sham exposure. And microbubbles were continuously injected during ultrasonic exposure/sham exposure. MI of therapeutic side for ultrasonic exposure in group A, B and C was 0.3, 0.7 and 1.1, respectively. After ultrasonic exposure/sham exposure, Doxorubicin concentration in vitro tumor tissue was detected, and then histological analysis was done. In addition, the range of peak negative pressure correspond with different MI were detected before ultrasonic exposure/sham exposure. Results Concentration of Doxorubicin of therapeutic side in group A was obviously higher than that of control side ([1.45±0.53]μg/g vs[1.07±0.46]μg/g; t=-5.163, P=0.001). In group B and C, there was no statistically significant difference of Doxorubicin concentration between therapeutic side and control side in the drug concentration (Z=-0.297, -0.357, P=0.766, 0.721). Quantitative analysis of CEUS showed that both PI and AUC increased obviously after ultrasonic exposure/sham exposure compared with those before exposure/sham exposure (all P<0.05), except for PI of control side in group B and AUC of control side in group B and C. Neither hemorrhage nor swelling was observed in tumor tissue of both sides in any group. The range of peak negative pressure correspond with MI of 0.3 (group A), 0.7 (group B) and 1.1 (group C) was 0.81-0.83 MPa, 0.96-1.32 MPa and 2.29-2.53 MPa, respectively. Conclusion DUS (MI=0.3) combined with microbubbles can enhance blood perfusion and improve the chemotherapeutic drug concentration of tumor tissues in nude mice bearing human pancreatic cancer. |
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