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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．
Objective: To study the effect of N-desulfated heparin on tumor metastasis, angiogenesis and expression of vascular endothelial growth factor (VEGF) in human gastric cancer with severe combined immunodeficiency (SCID). Methods: The SCID mouse model of orthotopic implantation of human gastric carcinoma was established and randomly divided into two groups. Transplantation of 1 wk, intravenous injection of normal saline (NS group) and N-desulfated heparin [10 mg / (kg · d)] (N-desulfated heparin group), 2 times / wk, 3 wk. The animals were sacrificed on the 6th week and the tumor metastasis was observed. The MVD and VEGF expression were detected by immunohistochemistry. Results: The rate of tumor metastasis in the saline group was 80% and that in the N-desulfated heparin group was 20%. There was a significant difference between the two groups (P <0.05). No side effects such as bleeding were found. The mean microvessel density in the saline group was 8.0 ± 3.1, and the mean microvessel density in the N-desulfated heparin group was 4.3 ± 1.8. Statistically, the difference between the two groups was significant (P <0.05). The positive rate of VEGF in NS group was significantly higher than that in N-desulfated heparin group (90% vs 20%, P <0.05). Conclusion: N-desulfated heparin can inhibit the metastasis of tumor by inhibiting VEGF expression and angiogenesis, and there is no obvious bleeding and other adverse reactions.