低频聚焦超声联合微泡治疗兔VX2原位肝癌移植瘤的疗效评价

The therapeutic effect of low frequency ultrasound mediated microbubbles destruction on rabbit VX2 orthotopic hepatic tumors

目的研究低频聚焦超声联合微泡对兔VX。原位肝癌移植瘤的治疗效果。方法将24只兔VX2原位肝癌移植瘤模型随机分为4组（6只／组）：①空白对照组（A组），仅注射生理盐水；②微泡对照组（B组），仅注射微泡造影剂；③超声辐照组（C组），注射生理盐水联合低频聚焦超声辐照；④超声辐照加微泡治疗组（D组），行微泡注射联合低频聚焦超声辐照。根据实验参数每组连续治疗3d，分别于治疗前、治疗后第1、7、14及21d行常规超声和超声造影检查，并对造影图像进行量化分析，记录各组治疗前后的肿瘤体积（TV）、造影峰值强度（PI）。观察期结束后处死实验兔并行组织病理学检查。结果治疗前各组TV与PI差异均无统计学意义（均P〉0．05）；治疗后第1d各组TV差异均无统计学意义（均P〉0．05），C、D组PI明显低于A、B组（均P〈0．05）；治疗后第7、14、21d，D组TV及PI均小于A、B、C组（均P〈0．05），A、B、C三组间比较差异均无统计学意义（均P〉0．05）。HE染色显示，D组肿瘤组织大部分坏死，有微血栓形成，并有局部出血，而A、B、C三组很少见到上述病理改变。结论低频聚焦超声联合微泡可有效抑制兔Vx。原位肝癌移植瘤的生长，是一种具有临床应用前景的非创伤性治疗肿瘤的新方法。

Objective To determine whether low frequency ultrasound mediated microbubbles destruction （UMMD） could inhibit VX2 orthotopic hepatic tumor growth in rabbit models. Methods Twenty-four New Zealand white rabbits were implanted with VX2 tumor in left hepatic lobe to establish a homograft rabbit model of liver neoplasms in situ, which were randomly divided into four groups（6 rabbits in each group）： group A （intravenous saline only）, group t~ （intravenous microbubbles only）, group C （intravenous saline ＋ low frequency focused ultrasound exposure）, and group D （intravenous microbuhhles ＋ low frequency focused ultrasound exposure）. After 3 days consecutive treatment, tumor volume（TV）, and peak intensity （PI） were monitored by conventional ultrasound and contrast enhanced ultrasound （CEUS） on 0, 1, 7, 14 and 21 days after treatment. The rabbits were euthanized at the end of the experiment. Tumor tissues were evaluated by HE stain. Results The parameters of TV and PI of each tumor had no significant difference among four groups before treatment （all P〉 0.05）. TV had no significant difference among four groups on 1 day after treatment（all P〈0.05） ;PI in group C and group D were significantly lower than those in group A and group B （all P 〈0.05）. TV and PI in group D were significantly smaller than those in other groups on 7, 14,21 days after treatment（all P 〈0.05）. There was no statistical difference in TV and PI among group A, group B and group C（all P〉0.05）. The pathological changes of necrosis tissue, hemorrhagic damage of microvessel and thrombosis were observed in the tumors of group D only, whereas these changes occurred rarely in other groups. Conclusions UMMD can inhibit the growth of VX2 hepatic tumors in rabbits, and be used as a promising novel therapeutic strategy to liver neoplasms.