去甲二氢愈创木酸对VEGF及其受体KDR基因表达影响的研究

目的：探讨去甲二氢愈创木酸（NDGA）对血管生成因子（VEGF）及其相应受体KDR基因表达状况的影响及其意义。方法：采用免疫组化、原位杂交及图像分析等技术方法观测NDGA作用下人恶性胶质瘤细胞系SHG－44细胞VEGF基因、人脐静脉内皮细胞系ECV－304细胞VEGF的相应受体KDR基因表达的变化。结果:①100μmol/L的NDGA处理胶质瘤细胞1－3d ，引起VEGF蛋白及mRNA表达水平的降低；②100μmol/L的NDGA处理内皮细胞1－3d，受体KDR的蛋白表达也呈下降趋势，且KDR基因表达的降 低较胶质瘤细胞VEGF的降低更为明显。结论：NDGA对胶质瘤细胞VEGF的表达有抑制作用，NDGA也抑制了内皮细胞KDR的表达，此抑制作用可能是NDGA抗血管生成的重要分子基础。

Effect of nordihydroguaiaretic acid on expressions of VEGF and its receptor KDR in vitro

Objective　To explore the effect of nordihydroguaiaretic acid (NDGA) on the expressions of vascular endothelial growth factor (VEGF) and its receptor, kinase-inserted domain containing receptor(KDR) and the possible mechanism. Methods　The expression of VEGF in human malignant glioma cell line SHG-44 and that of KDR in human umbilical vein endothelial cell (HUVEC) line ECV-304 were observed 1～3 d after NDGA treatment with immunohistochemistry, in situ hybridization and image analysis. Results　The expression of VEGF was declined at protein or mRNA levels in SHG-44 cells after treated with 100 μmol/L NDGA for 1 to 3 d. The expression of KDR in endothelial cells with 100 μmol/L NDGA treatment for 1 to 3 d was decreased too, in a more obvious way compared with the decline of VEGF expression in SHG-44 cells. Conclusion　The results suggest that NDGA inhibits the expression of VEGF in glioma cells as well as that of VEGF receptor KDR in endothelial cells, which may be the important molecular mechanism of anti-angiogenesis of NDGA.