摘要
目的利用DCE-MRI监测血管内皮生长因子(VEGF)反义核酸调控兔后腿VX2肿瘤早期血管生成的效果,评价反义基因抗血管生成治疗价值以及无创性影像监测方法。方法利用分子生物学方法构建兔VEGF反义基因真核表达载体。将30只新西兰大白兔,平均分5组(A、B、C组为治疗组,D、E组为对照组),建立后腿接种VX2肿瘤模型。采用两种反义基因导入方法,于最后一次反义基因导入后0、3、7天分别对各组动物行DCE-MRI检查,计算第一分钟最大强化斜率。采用Western Blot和免疫组织化学染色法分析肿瘤组织VEGF表达。结果与对照组比较,A组(治疗后0、3、7天)、B、C组(治疗后7天)肿瘤体积减小(P<0.05);A组(治疗后0天)、B、C组(治疗后3天)第一分钟最大强化斜率显著减低(P<0.01);A、B、C组VEGF表达明显减低(P<0.01)。结论①VEGF反义核酸可早期有效抑制兔VX2肿瘤VEGF表达,减少肿瘤血管形成,对肿瘤的生长具有抑制作用。②DCE-MRI可用于监测抗血管治疗早期血管通透性变化。
Objective To evaluate the anti-angiogenie effect of antisense vascular endothelial growth factor （VEGF） eDNA on rabbit VX2 tumor model in the hind leg by dynamic contrast-enhanced MR imaging （DCE-MRI）. Methods Eukaryotic expression vector of rabbit antisense VEGF cDNA was eonstrueted using moleculor biology technique. Thirty New Zealand white rabbits were divided into 5 groups （group A, B, C with antisense VEGF gene, and group D, E as eontrol groups）. DCE-MR images were acquired using a 3D spoiled gradient echo pulse sequence. The steepest slope of enhancement in the first minute was ealculated. Western Blot and immunohistochemical stain （IHS） were used to assay VEGF expression of tumor tissue. Results Compared with control groups （D and E）, the size of tumors were significantly decreased on 0, 3, 7 days after intervention in group A and （P〈0.05） and on day 7 in group B and C （P〈0.05）. The DCE-MRI parameter （SS） was significantly decreased in group B and C on day 3 after intervention （P〈0.01） and on day 0, 3 in group A. Western Blot and IHS assay showed that the VEGF expression were decreased in group A, B and C. Conclusion ①Antisense VEGF eDNA can inhibit the VEGF expression of VX2 tumors effectively in early stage and inhibit tumor growth. ②The semi-quantitative parameters of DCE-MRI can be used effectively on surveillance of the early pathophysiological ehanges of the antian giogenesis therapy.
出处
《中国医学影像技术》
CSCD
北大核心
2005年第11期1640-1643,共4页
Chinese Journal of Medical Imaging Technology
基金
国家自然科学基金资助(30170286)
关键词
反义核酸
血管内皮生长因子
VX2肿瘤
磁共振成像
图像增强
Antisense cDNA
Vascular endothelial growth factor
VX2 tumor
Magnetic resonance imaging
Image enhancement
