动态增强磁共振监测VEGF反义核酸对兔颌面部VX2肿瘤放疗的增敏作用

Effect of VEGF Antisensenucleic Acids on Rabbit VX2 Maxillofacial Tumor with Radiation Therapy by Dynamic Contrast Enhanced Magnetic Resonance Imaging

目的:研究动态增强磁共振成像(dynamic contrast enhanced magnetic resonance imaging,DCE-MRI)监测VEGF反义核酸对兔颌面部VX2肿瘤放疗后的影响。方法:24只颌面部VX2荷瘤兔模型随机分4组:放疗组(A组):给予16Gy放疗;VEGF反义核酸治疗组(B组):肿瘤局部注入VEGF反义核酸150μg;VEGF反义核酸联合放疗组(C组):16Gy放疗后立即局部肿瘤内注射VEGF反义核酸150μg;对照组(D组):肿瘤内注射300μl5%葡萄糖水溶液。治疗后第3天、14天分别行DCE-MRI检查,计算MER(Maximal enhancement ratio,最大强化率)及SLE(Slope of enhancement,强化率斜率)值,14天处死动物行病理检查和VEGF免疫组化染色。结果:C组治疗后14天肿瘤体积明显缩小,与治疗前和治疗后三天及其它组比较差别具有统计学意义(P<0.01)。MER值降低和SLE值降低,与治疗前比较差别有统计学意义(P<0.05)。病理切片显示肿瘤细胞水肿、出血,坏死,血管壁增厚闭塞,VEGF免疫阳性表达下降,经IHS评分与A组和D组差别有统计学意义(P<0.05)。结论:放疗后立即肿瘤内注射VEGF反义核酸可通过降低VEGF表达从而增强放疗的早期疗效,DCE-MRI可作为可靠的活体检测手段。

Objective： To study effect of vascular endothelial growth factor （VEGF） antisensenucleic acids on rabbit VX2 maxillo -facial tumor with radiation therapy by dynamic contrast enhanced magnetic resonance imaging （DCE-MRI）. Materials and Methods： 24 rabbits with VX2 tumor model of maxillofacial were randomly divided into 4 groups（n=6）. Group A： made with 16 Gy irradiation. Group B： injected with 150 p g VEGF antisense in tumor.Group C： made with 16 Gy irradiation just before the injection of 150 μg VEGF antisense cDNA in tumor. Group D： injected with 5 % dextrose in water. DCE-MRI was performed on the 3 day and 14 day after the treatment and MER and SLE value were calculated. Specimens were harvested and HE staining and VEGF immunohistochemical staining were performed after the last MRI examination. Results： Volume of tunors in group C was reduced obviously after treatment, there was significant statistical difference compared with pre-treatment, 3 days after treatment, and other groups （P〈0.01 ）. MER and SLE value in group also decreased and there was significant statistical difference compared with pre-treatment. The pathological section result indicated cellular edema, hemorrhage, necrosis and thickening or occlusion of vascular wall in tumor issue. The expressions of VEGF in group C were decreased and there was significant statistical difference compared with group A and D （P〈0.05）after immunohistochemical scores. Conclusions： VEGF antisense plasid can improve therapeutic effect of radiotherapy by intratumor injection shortly after radiation therapy through decreased the expression of VEGF, and DCE-MRI can be used as a reliable monitoring tools in vivo.