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中华医学超声杂志（电子版）

中华医学超声杂志（电子版） ›› 2021, Vol. 18 ›› Issue (07) : 705 -709. doi: 10.3877/cma.j.issn.1672-6448.2021.07.017

基础研究

超声联合微泡对兔VX2肿瘤化疗效果的影响
刘娅1, 刘政1,†(), 冯爽1, 董睿1, 陈晓琴1, 益磋1   
  1. 1. 400037　重庆，陆军军医大学附属新桥医院超声科
  • 收稿日期:2020-03-28 出版日期:2021-07-01
  • 通信作者: 刘政
  • 基金资助:
    国家重点研发计划数字诊疗装备研发重点专项(2017YFC0107300)

Effects of ultrasound combined with microbubbles on tumor in rabbits bearing VX2 tumors undergoing chemotherapy

Ya Liu1, Zheng Liu1(), Shuang Feng1, Rui Dong1, Xiaoqin Chen1, Cuo Yi1   

  1. 1. Department of Ultrasound, Xinqiao Hospital, the Army Medical University, Chongqing 400037, China
  • Received:2020-03-28 Published:2021-07-01
  • Corresponding author: Zheng Liu
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引用本文：

刘娅, 刘政, 冯爽, 董睿, 陈晓琴, 益磋. 超声联合微泡对兔VX2肿瘤化疗效果的影响[J]. 中华医学超声杂志（电子版）, 2021, 18(07): 705-709.

Ya Liu, Zheng Liu, Shuang Feng, Rui Dong, Xiaoqin Chen, Cuo Yi. Effects of ultrasound combined with microbubbles on tumor in rabbits bearing VX2 tumors undergoing chemotherapy[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2021, 18(07): 705-709.

目的

探讨诊断超声联合微泡在增强兔VX2肿瘤化疗的同时，对肿瘤生长、肿瘤多器官转移及动物生存期的影响。

方法

将陆军军医大学附属新桥医院动物实验中心符合实验条件的41只皮下VX2荷瘤兔随机分为A（n=14）、B（n=14）、C（n=13）3组。各组均经耳缘静脉注射阿霉素1.0 mg/kg进行治疗，同时，A组行高机械指数（0.7~0.8）超声联合微泡照射，B组行低机械指数（0.2~0.3）超声联合微泡照射，C组进行超声假照，采取隔天治疗的方式治疗，每组治疗3次。二维超声测量各组治疗第1、3、5、8、11、14、17、20、23、26、29、32 d肿瘤最大切面横径（a）及短径（b），计算肿瘤体积，绘制肿瘤生长曲线并做比较，3组肿瘤生长趋势比较采用重复测量数据的方差分析，至实验终结时，采用χ2检验比较各组多器官转移情况，采用One-way ANOVA检验比较荷瘤兔的生存期情况。

结果

治疗后，B组肿瘤生长趋势明显低于C组，差异具有统计学意义（P=0.031），A组与C组、A组与B组肿瘤生长趋势比较，差异均无统计学意义（P均＞0.05）。A、B、C组荷瘤兔生存期分别为（100.00±29.61）d、（94.93±36.92）d、（118.92±48.41）d，差异无统计学意义（F=1.146，P=0.255）。A、B、C组中分别有6只（42.90%）、4只（28.60%）、6只（46.20%）荷瘤兔发生多器官转移，器官转移率比较，差异无统计学意义（χ2=1.007，P=0.604）。

结论

低机械指数超声联合微泡在增强兔VX2肿瘤化疗的同时，可抑制肿瘤生长，暂未发现有促进多器官远处转移及缩短荷瘤兔生存期。

关键词: 超声, 化疗, VX2肿瘤, 转移, 生存期
Objective

To explore the effect of diagnostic ultrasound combined with microbubbles on tumor growth, metastasis rate, and animal survival in rabbits bearing VX2 tumors undergoing chemotherapy.

Methods

Forty-one male rabbits bearing subcutaneous VX2 tumors from Laboratory Animal Center, Xinqiao Hospital, The Army Medical University were randomized into three groups: A (n=14), B (n=14), and C (n=13). All animals were given an intravenous administration of doxorubicin at 1 mg/kg. Animals in group A were additionally treated by high mechanical index (0.7-0.8) ultrasound combined with microbubbles (HUSM), group B was treated by low mechanical index (0.2-0.3) ultrasound combined with microbubbles (LUSM), and group C was treated by sham ultrasound. All the groups were treated every other day for a total of three times. The longest diameter and shortest diameter of the tumor were measured at 1 d, 3 d, 5 d, 8 d, 11 d, 14 d, 17 d, 20 d, 23 d, 26 d, 29 d, and 32 d to calculate tumor volume and plot tumor growth curve, which was compared by repeated measures analysis variance. At the end of the study, the multi-organ metastasis rate and survival time of rabbits were observed and compared by χ2 test and one-way ANOVA, respectively.

Results

After treatment, the tumor growth trend in group B was significantly lower than that of group C (P=0.031), but there was no statistically significant difference between groups A and C and between groups A and B (P＞0.05). The mean survival time of rabbits in groups A, B, and C was (100.00±29.61) days, (94.92±36.92) days, and (118.92±48.41) days, respectively; there was no significant difference among them (F=1.146, P=0.255). Six (42.90%), four (28.60%), and six (46.20%) rabbits developed multi-organ metastasis in groups A, B, and C, respectively; the effect of different treatments on distant metastasis rate had no significant difference (χ2=1.007, P=0.604).

Conclusion

LUSM can enhance chemotherapy effects and inhibit tumor growth while not promoting multi-organ metastasis or shortening the survival of rabbits.

Key words: Ultrasound, Chemotherapy, VX2 tumor, Metastasis, Survival
图1 二维超声观察治疗第1、5、14、23、32天A、B、C组VX2皮下荷瘤兔肿瘤大小。A、B、C组治疗后肿瘤体积均有增大趋势，但B组增长趋势小于A、C组。治疗第14、23、32天，可见B组肿瘤体积明显小于A、C组，且第23、32天A、C组肿瘤较大，内部均出现明显液化坏死
图2 A、B、C组VX2皮下荷瘤兔肿瘤生长曲线。A、B、C组肿瘤总体生长趋势为C组＞A组＞B组，A、C组生长曲线呈持续上升，3次治疗后，第5~11天A、C组肿瘤生长较缓慢，B组可见肿瘤体积缩小，随后A、B、C 3组肿瘤体积均呈不同程度增长，但B组上升趋势明显低于C组
图3 A、B、C组荷瘤兔多器官远处转移大体标本。图a双肺见多处转移，转移灶呈白色实性组织，与周围正常肺部组织分界欠清晰；图b为肝多处转移，肝内见白色散在转移灶；图c为肾内较大转移灶，内部可见呈融合状
图4 A、B、C组荷瘤兔生存期柱状图。3组瘤兔生存期比较，差异无统计学意义（P＞0.05）
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