TACE联合血管内皮抑素治疗兔VX2肝癌CT灌注与肿瘤血管生成的分析

TACE combined with endostatin for the treatment of rabbit VX2 hepatic carcinoma:an analysis of the correlation between CT perfusion parameters and tumor angiogenesis

目的探讨经肝动脉化疗栓塞术(TACE)联合血管内皮抑素(Rh-endostatin)治疗兔VX2肝癌的疗效,并分析治疗前后肿瘤周边的CT灌注参数与微血管密度(MVD)、血管内皮生长因子(VEGF)表达之间的相关性。方法建立30只兔VX2肝癌模型,随机分为3组,每组10只。A组:单纯TACE组;B组:TACE+内皮抑素组;C组:对照组,灌注生理盐水。3组于治疗前后均行CT灌注扫描,获取灌注参数肝血流量(HBF)、血容量(HBV)、肝动脉指数(HAF)、毛细血管表面通透性(PS)。各组于第1次灌注扫描后分别处死1只肿瘤兔,介入治疗后10d行第2次灌注扫描,并处死所有肿瘤兔。利用免疫组化检测MVD、VEGF的表达情况。结果治疗前3组肿瘤周边CT灌注参数HBF、HBV、HAF、PS值差异无统计学意义(P>0.05),治疗后A、B两组均有明显降低,B组较A组明显增高;B组中MVD、VEGF较A、C组显示减低,A组MVD、VEGF较C组稍显增高(P<0.05)。3组中肿瘤VEGF与MVD均呈显著正相关(P<0.05),B组中HBF、HBV、HAF、PS分别与MVD、VEGF呈正相关(P<0.05),而A、C组中HBF、HBV、HAF、PS与MVD、VEGF无相关性(P>0.05)。结论 TACE联合内皮抑素治疗兔VX2肝癌与单纯TACE比较,可明显降低VEGF的表达,显著地抑制治疗后肿瘤新生血管的形成,从而减慢肿瘤的生长速度。

Objective To explore the efficacy of transcatheter arterial chemoembolization （TACE） combined with endostatin （Rh-endostatin） in treating rabbit VX2 hepatic carcinoma,and to discuss the correlation between CT perfusion parameters and the expressions of microvascular density （MVD） as well as vascular endothelial growth factor （VEGF） before and after the treatment.Methods The experimental model was established in 30 rabbits,which were randomly and equally divided into 3 groups.Group A,receiving TACE only.Group B,receiving both TACE and Rh-endostatin.Group C （control group）,receiving saline only.CT perfusion scanning was performed in all three groups three days before and at different points of time after the treatment.The perfusion parameters,including HBF,HBV,HAF and PS,were determined.One rabbit from each group was sacrificed after the first CT perfusion scanning.Ten days after the interventional therapy the second CT perfusion scanning was carried out,then all the VX2 tumor-bearing rabbits were killed.The expression of MVD and VEGF were determined with immunohistochemistry method.Results Before therapy,the difference in perfusion parameters （HBV,HBF,HAF and PS） among three groups was of no statistical significance （P 0.05）.After the treatment,the perfusion parameters were markedly decreased,although the perfusion parameters in group B were significantly higher than that in group A.MVD and VEGF in group B were obviously lower than these in group A and group C,while MVD and VEGF in group A were slightly higher than these in group C （P 0.05）.A positive correlation existed between VEGF and MVD in all three groups （P 0.05）.In group B,HBV,HBF,HAF and PS showed a positive correlation with VEGF and MVD （P 0.05）,while in group A and C no definite relationship existed between the perfusion parameters （HBV,HBF,HAF and PS） and VEGF or MVD （P 0.05）.Conclusion In treating rabbit VX2 hepatic carcinoma TACE combined with Rh-endostatin can significantly reduce the expression level of VEGF and effectively inhibit the formation of the tumor vessels,in this way the growth of tumor can be restrained.