大鼠Walker-256微小转移性肝癌CT灌注参数与微血管密度及血管内皮生长因子表达关系的研究

目的应用CT灌注成像观察大鼠微小转移性肝癌所引起的血流动力学变化与肿瘤血管化程度的相关性。方法22只经脾脏注入Walker-256(细胞含量2×107)制备成肝脏微小转移癌的大鼠为实验组;10只大鼠经脾脏注入等量生理盐水为对照组。实验组中随机选取10只作为空白对照组。CT灌注扫描后使用斜率法得到参数包括:肝动脉灌注量、门静脉灌注量、肝灌注指数、总肝灌注量。采用免疫组织化学方法测定病理标本的微血管密度和血管内皮生长因子。结果实验组中有19只大鼠发现转移灶,直径在0.5~6.6 mm之间。各项参数值组间比较:实验组大鼠肝动脉灌注量、肝灌注指数明显高于对照组和空白组;对照组和空白组之间无显著差别。实验组门静脉灌注量明显低于对照组和空白组,对照组和空白组无显著差别。总肝灌注量组间比较,三组之间没有差别。VEGF表达程度随着实验组大鼠肝动脉灌注量增高而增高。而且VEGF不同表达程度的转移癌之间MVD的差异均有统计学差异。结论大鼠微小肝转移癌表现为肝动脉灌注量的增加和门静脉灌注量的降低。肝动脉灌注量的大小与VEGF的表达程度和MVD呈正相关。

Correlation study between MVD,expression of VEGF and CT perfusion parameters in small metastases of rat liver

Objective Using CT perfusion imaging to evaluate the correlation between hemodynamic changes caused by hepatic micrometastases in rats and extent of tumor angiogenesis in pathologic specimens. Methods Liver micrometastases were produced in 22 SD rats by transspleenic injection of 2×10⁷ Walker-256 cells. Ten experimental control rats were injected with saline solution. CT perfusion was performed to calculate liver perfusion by gradient method. Perfusion parameters included hepatic artery perfusion, portal venous perfusion, total hepatic blood flow and hepatic perfusion index. MVD and expressions of VEGF were examined by immunohistochemical techniques. Results The micrometastases (diameter, between 0.5 mm and 6.6 mm) were seen in 19 rats. Hepatic arterial perfusion was 2.25 times in the rats with micrometastases than that in the control rats. Portal hepatic perfusion was 76.6% lower in the rats with micrometastases than that in the control rats. The MVD and expressions of VEGF of tumor were positive linear correlation with hepatic artery perfusion. Conclusion Small liver metastases in rats can lower the portal perfusion and increase the arterial perfusion. There were positive linear correlation between MVD and expressions of VEGF with hepatic artery perfusion.