颌面部VX2肿瘤DCE-MRI与乏氧程度及VEGF表达的相关性研究

目的分析颌面部VX2肿瘤DCE-MRI动态曲线与肿瘤乏氧染色和血管内皮生长因子(VEGF)表达水平的相关性,探讨DCE-MRI在肿瘤乏氧评价中的价值.方法 8只新西兰大白兔于单侧颌面部咬肌内接种VX2肿瘤细胞0.5 ml,接种后10天开始,每隔2天取一只荷瘤兔行DCE-MRI检查,绘制肿瘤动态增强曲线,计算最大强化率(MER)和强化率斜率(SLE)值.对处死的荷瘤兔,取对应层面病理标本行HE染色、乏氧染色和VEGF染色分析.结果 8只实验兔成瘤率达100%,肿瘤位于单侧咬肌内,呈实质性,边缘较清晰;肿瘤MER值与乏氧程度行Spearman's等级相关分析存在显著负相关(P<0.01);肿瘤SLE值与VEGF表达水平存在正相关(P<0.05).对肿瘤乏氧染色及VEGF表达行连续切片对照研究,发现乏氧染色阳性的区域,VEGF表达也相对较高;但VEGF表达阳性区并不完全与肿瘤乏氧区表达一致.结论肿瘤乏氧与VEGF表达关系密切,乏氧可诱导VEGF表达的增高,而VEGF表达能促进肿瘤血管生成.DCE-MRI动态增强参数与肿瘤乏氧程度和VEGF表达水平有很好的相关性.

DCE-MRI study of maxillofacial VX2 tumors and its relationship between tumor hypoxia and VEGF expression

Objective To analyze the correlation of dynamic contrast-enchanced MR imaging (DCE-MRI) with tumor hypoxia and vascular endothelial growth factor (VEGF) expression and to evaluate the value of DCE-MRI in tumor hypoxia imaging. Methods Eight New Zealand rabbits were inoculated with 0.5 ml (1×10⁸/ml) VX2 tumor cells in the maxillofacial masseter. DCE-MRI was performed every 2 days since the 10th day on. The maximal enhancement ratio (MER) and slope of enhancement (SLE) were calculated. After DCE-MRI, the rabbit was sacrificed and the corresponding tumor specimen was harvested. HE staining, hypoxia and VEGF immunohistochemical staining were carried out. Results All the 8 rabbits had tumors growing. The masses located in the unilateral masseters, and had relatively clear margins. MER had a negative correlation with tumor hypoxia degree (P<0.01). SLE bore a positive correlation with VEGF immunohistochemical score (P<0.05). We compared the continuous sections of hypoxia with VEGF staining of the tumor, and found that where the more hypoxia staining positive, the stronger VEGF expression. But VEGF staining was not always coincident with the staining of hypoxia. Conclusion Tumor hypoxia had a close relationship with the expression of VEGF, and VEGF could promote tumor angiogenesis. DCE-MRI had a good correlation with tumor hypoxia degree and VEGF expression.