VEGF反义寡核苷酸抑制荷瘤大鼠胶质瘤血管生成的作用和效果

INHIBITORY EFFECT ON ANGIOGENESIS AND GLIOMA GROWTH OF TUMOR-BEARING RATS OF VEGF ANTISENSE OLIGONUCLEOTIDE

观察在荷瘤大鼠脑内原位注射血管内皮生长因子(VEGF)反义寡核苷酸对胶质瘤的血管生成的抑制效果。所有大鼠均在立体定向导引下右尾状核区接种含C6胶质瘤细胞 1× 10 6的Hank液 (2 0 μl)。实验Ⅰ和Ⅱ组在细胞接种后的 1和 2周各原位注射 1次 ,共 2次 ,每次实验Ⅰ组为 10 0 0 μmol/L、实验Ⅱ组为2 0 0 0 μmol/L的VEGF反义寡苷核酸。对照组仅在接种后第 1和 2周原位注射 2 0 μl的Hank液。第 3周时处死所有大鼠 ,观察肿瘤的生长情况 ,标本做常规HE染色和免疫组化染色检查VEGF的表达和血管密度 (MVD) ;原位杂交观察VEGFmRNA的表达。结果显示 ,实验组大鼠有较好的生存状态 ,而对照组在实验 2周时开始出现颅内高压症状 ,至 3周时大鼠大多处于濒危状态 ;成瘤抑制率实验Ⅰ组为 91 5 % ,实验Ⅱ组为 10 0 % ;实验组和对照组VEGFmRNA、VEGF的表达和微血管密度比较差异有显著性意义。研究表明 。

To observe the inhibitory effects of VEGF antisense oligonuoleotide on angiogenesis and glioma growth of tumor bearing rats. 1×10 6 C 6 glioma cells(20μl) were seeded with high flow microinfusion into right caudate nucleus of all rats with sterotactic technique. In the treatment groups Ⅰ and Ⅱ 1 000 μmol/L, 2 000 μmol/L VEGF antisense oligonucleotide was respectively given at the site of seeding twice 1 and 2 weeks after cell inoculation. The control group received only 20μl Hank′s solution twicely. Three weeks after cell inoculation, the general condition of the treated rats were better, while rats in control group were in precarious conditions. The inhibition rate of tumor growth was 91 5% in the treated group Ⅰ, 100% in the treated group Ⅱ. The expressions of VEGF mRNA, VEGF, and MVD were significantly different between treatment and control groups. The results indicated that VEGF was required for the maintenance of angiogenesis in the tumor, and inhibition of VEGF might be a therepeutic strategy in the treatment of glioma.