N-去硫酸肝素对SCID小鼠胃癌血管生成和VEGF表达的影响  

Effect of N-desulfated heparin on angiogenesis and vascular endothelial growth factor expression in mice with severe combined immunodeficiency

作　　者：陈金联[1] 陆金来[1] 陈明祥[1] 陈维雄[1] 朱金水[1] 陈尼维[1] 陈国强[2] 耿建国[3] 

机构地区：[1]上海交通大学附属第六人民医院消化科,上海市200233 [2]中国科学院上海实验动物中心,上海市200031 [3]中国科学院上海细胞生物学研究所,上海市200031

出　　处：《世界华人消化杂志》2005年第22期2685-2688,共4页World Chinese Journal of Digestology

基　　金：上海市卫生局面上基金资助课题.No.034045

摘　　要：目的:研究N-去硫酸肝素对人胃癌重度联合免疫缺陷(SCID) 小鼠转移模型肿瘤转移抑制、血管生成和血管内皮生长因子(VEGF)表达的影响．方法:建立人胃癌组织原位移植SCID小鼠转移模型,随机分成两组．移植1 wk,分别从静脉内注射生理盐水(生理盐水组) 与N-去硫酸肝素[10 mg／(kg·d)](N-去硫酸肝素组),2次／wk, 共3 wk．第6 wk处死动物,观察肿瘤转移情况,免疫组化方法检测肿瘤组织微血管密度(MVD)、VEGF的表达．结果:生理盐水组肿瘤转移率为80%,N-去硫酸肝素组转移率为20%,两组之间差异有统计学意义(P<0．05)．未发现出血等副作用．生理盐水组平均微血管密度为8．0±3．1,N-去硫酸肝素治疗组平均微血管密度为4.3±1．8．经统计学处理,两组之间差别有显著意义(P<0．05)．生理盐水组VEGF阳性表达率明显高于N-去硫酸肝素治疗组,分别为90％与20％(P<0．05)．结论:N-去硫酸肝素通过抑制肿瘤组织VEGF表达和血管生成,从而抑制肿瘤的转移,并且无明显出血等不良反应．AIM： To investigate the effect of N-desulfated heparin on tumor metastasis, angiogenesis, and expression of vascular endothelial growth factor （VEGF） after orthotopic implantation of human gastric carcinoma in mice with severe combined immunodeficiency （SCID）. METHODS： The SCID mice metastasis model was established by in situ implantation of human gastric carcinoma tissue, then the mice were randomly divided into two groups： the normal saline group （treated with normal saline） and NNH group [treated with N-desulfated heparin, 10 mg/（kg-d） iv, 2/wk, for 3 wk]. The mice were sacrificed 6 wk after the implantation. The tumor metastasis, intratumoral microvessel density （MVD）, and VEGF expression were evaluated respectively.RESULTS： The tumor metastasis rates were significantly different between normal saline and NNH group （80% vs 20%, P 〈0.05）. No side effect such as hemorrhage was observed in the mice. The MVD was 8.0±3.1 in the normal saline group and 4.3±1.8 in the NNH group, and there was significant difference between those 2 groups （P 〈0.05）. The positive rate of VEGF expressi- on was significantly higher in the normal saline group than that in the NNH group （90% vs 20%, P 〈0.05）. CONCLUSION： N-desulfated heparin can inhibit the metastasis of gastric cancer through inhibiting the expression of tumor VEGF and angiogenesis with no obvious side effect such as hemorrhage.

关 键 词：N-去硫酸肝素 胃癌转移 血管生成 血管内皮生长因子 

分 类 号：R735.2[医药卫生—肿瘤]