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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 the effect of VEGF antisense nucleic acid on the VX2 tumor in maxillofacial region of the rabbit after radiotherapy by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Methods: Twenty-four maxillofacial VX2 tumor-bearing rabbits were randomly divided into 4 groups: radiotherapy group (group A): 16Gy radiotherapy; VEGF antisense nucleic acid group (group B): VEGF antisense oligonucleotide Group C: 16 Gy intracitric injection of VEGF antisense oligonucleotide immediately after radiotherapy; control group (Group D): intratumoral injection of 300 μL of 5% dextrose in water. DCE-MRI was performed on the third day and the 14th day after treatment to calculate the Maximal enhancement ratio (MER) and Slope of enhancement (SLE), and the animals were sacrificed on the 14th day for pathological examination and VEGF immunohistochemistry Staining. Results: The tumor volume of Group C decreased significantly 14 days after treatment, which was significantly different from that before treatment, three days after treatment and other groups (P <0.01). The decrease of MER value and the decrease of SLE value were statistically significant compared with those before treatment (P <0.05). Pathological sections showed tumor cell edema, hemorrhage, necrosis, occlusion of vascular wall thickening, and decreased VEGF immunoreactivity. The difference between IHS and A group and D group was statistically significant (P <0.05). CONCLUSION: Intravenous injection of antisense VEGF RNA immediately after radiotherapy can enhance the early effect of radiotherapy by decreasing the expression of VEGF. DCE-MRI can be used as a reliable means of in vivo detection.