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目的探讨兔肝VX2移植瘤经肝动脉化学治疗栓塞术(TACE)瘤周抗血管生成的可行性。方法 30只成年新西兰大白兔,雌雄不限,体质量2~3 kg。用VX2鳞癌制作肝癌移植瘤模型。随机分为实验A组、实验B组和阳性对照C组(每组10只)。实验A组行TACE过度栓塞结合索拉非尼超声微泡治疗,实验B组行TACE过度栓塞结合索拉非尼治疗,阳性对照C组行灌喂0.9%氯化钠溶液和TACE过度栓塞。治疗4周后,行MSCT检查,计算碘油沉积的体积(V_I)和残瘤灶的体积(V_R),然后取实验兔标本均行免疫组织化学检测血管内皮生长因子(VEGF)的表达强度。结果实验A组VI为(4.5±2.1)cm~3,明显大于实验B组和阳性对照C组[(1.5±1.8)cm~3、(1.4±1.2)cm~3;P<0.01],但实验B组和阳性对照C组差异无统计学意义(P>0.05)。实验A组V_R为(2.8±2.7)cm~3,明显小于实验B组和阳性对照C组[(5.1±3.8)cm~3、(8.9±4.6)cm~3;P<0.05、P<0.01];实验B组也明显小于阳性对照C组(P<0.05)。实验A组没有发现肝内外转移,实验B组3只发现肝内外转移,而阳性对照C组10只均发现肝内外转移。实验A组、实验B组及阳性对照C组平均VEGF表达强度值分别为0.11±0.06、0.21±0.08、1.48±0.32。实验A组明显低于阳性对照C组(t=5.14,P<0.001),实验B组明显低于阳性对照C组(t=3.36,P<0.001)。结论兔肝VX2移植瘤经索拉非尼微泡造影剂增强脉冲式聚焦超声组织毁损术和TACE过度栓塞,在瘤周可形成抗血管生成屏障。
Objective To investigate the feasibility of anti-angiogenesis in rabbit peri-revascularization of hepatic VX2 transplanted tumor by transcatheter arterial chemoembolization (TACE). Methods Thirty adult New Zealand white rabbits were male and female with body weight of 2 ~ 3 kg. Liver cancer xenograft model was made with VX2 squamous cell carcinoma. Randomly divided into experimental group A, experimental group B and positive control group C (each group 10). In group A, TACE was over-embolized combined with sorafenib ultrasound microbubbles. In group B, TACE was over-embolized combined with sorafenib. In group C, 0.9% sodium chloride solution and TACE over-embolization were performed in group C. After 4 weeks of treatment, MSCT was performed to calculate the volume of lipiodol deposition (V_I) and the size of residual tumor (V_R). The expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemical staining. Results In the experimental group A, the VI was (4.5 ± 2.1) cm ~ 3, significantly higher than that in the experimental group B and the positive control group C [(1.5 ± 1.8) cm ~ 3, 1.4 ± 1.2 cm ~ 3; P <0.01] There was no significant difference between experimental group B and positive control group C (P> 0.05). The V_R in experimental group A was (2.8 ± 2.7) cm ~ 3, which was significantly lower than that in experimental group B and positive control group [(5.1 ± 3.8) cm ~ 3 and [8.9 ± 4.6] cm ~ ]; Experimental group B was also significantly less than the positive control group C (P <0.05). There was no intrahepatic or extrahepatic metastasis in experimental group A, intrahepatic and extrahepatic metastasis in three groups in experimental group B, and intrahepatic and extrahepatic metastases in group C of positive control group. The average VEGF expression of experimental group A, experimental group B and positive control group C were 0.11 ± 0.06, 0.21 ± 0.08, 1.48 ± 0.32, respectively. The experimental group A was significantly lower than the positive control group C (t = 5.14, P <0.001), and the experimental group B was significantly lower than the positive control group C (t = 3.36, P <0.001). Conclusion Rabbit liver VX2 xenografts enhanced by sorafenib microbubble contrast agent in pulsed focal ultrasound tissue and TACE over embolization can form anti-angiogenic barrier in the tumor.