兔肝癌肝动脉栓塞后肿瘤血管生成的变化

Angiogenesis in rabbit hepatic tumor after transcatheter arterial embolization

目的 观察肝癌肝动脉栓塞后肿瘤组织血管生成的变化。方法 建立兔肝癌模型 ,随机分栓塞组 (n =10 )和对照组 (n =10 )。于接种后 14d经肝动脉注入超液化碘油 (栓塞组 )或等量生理盐水 (对照组 )。栓塞后第 7天取肿瘤 ,免疫组织化学方法检测肿瘤组织微血管密度 (MVD)及血管内皮生长因子 (VEGF)蛋白的表达 ,逆转录 聚合酶链反应 (RT PCR)检测VEGFmRNA的表达。结果 栓塞组MVD (2 8.6± 10 .6)与对照组 (16.3± 6.9)比较差异有非常显著性 (t =3 .0 83 ,P <0 .0 1) ;栓塞后VEGF蛋白 (t =3 .0 75 ,P <0 .0 1)及VEGF165mRNA (t =3 .95 4,P <0 .0 0 1)表达水平显著增高 ;在栓塞组和对照组 ,VEGF蛋白表达均与MVD呈正相关 (r分别为 0 .69和 0 .72 ,P <0 .0 5 )。结论 肝动脉栓塞术可通过促使肿瘤细胞VEGF表达上调 ,从而促进肿瘤的血管生成 ,如果将介入栓塞与抗血管生成治疗相结合 。

Objective To study the influence of transcatheter arterial embolization on angiogenesis of hepatic tumor.Methods The rabbit hepatic tumor model was established.The animals were randomly divided into two groups (n=10 in each group).Fourteen days later,a silicon catheter was inserted into the left hepatic artery of rabbit with hepatic tumor and infusion was performed via the hepatic artery using Lipiodol (the treatment group) or saline (the control group).Rabbits were sacrificed 7 days after infusion and tumor tissues were taken out.The expression of vascular endothelial growth factor (VEGF) protein and microvessel density (MVD) of tumors were examined using immunohistochemistry.Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the VEGF mRNA expression of tumors.Results MVD was higher in the treatment group than in the control group (28.6± 10.6 vs 16.3± 6.9, t= 3.083, P< 0.01). Average absorbance value of VEGF in the treatment group was 0.162± 0.018, significantly higher than in the control group (0.142± 0.010, t= 3.075, P< 0.01). The expression level of VEGF165 mRNA was significantly higher in the treatment group than in the control group (2.58± 0.42 vs 1.99± 0.21, t= 3.954, P< 0.001). MVD was positive correlated to the VEGF expresion in both the treatment group (r= 0.69, P< 0.05) and the control group (r= 0.72, P< 0.05). Conclusion Transcatheter arterial embolization promotes the development of neovascularization of residual tumors after the embolization through up-regulation of the VEGF expression.The combination of transcatheter arterial embolization and antiangiogenic therapy can improve the effectiveness of transcatheter arterial embolization in the treatment of hepatocellular carcinoma.