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目的研究N-去硫酸肝素对人胃癌组织原位移植非肥胖性糖尿病(non-obesity diabetes,NOD)重度联合免疫缺陷(SCID)小鼠转移模型的肿瘤转移抑制、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NOD SCID小鼠胃痛转移模型,20只小鼠均分成2组。移植后1周,分别静脉注射0．9%氯化钠溶液(0．9%氯化钠溶液组)与10 mg/kg N-去硫酸肝素(N-去硫酸肝素组),每周2次,共3周。第6周处死动物,观察肿瘤转移情况,免疫组化法检测肿瘤组织微血管密度、VEGF表达,荧光定量PCR检测肿瘤组织VEGF mRNA表达。结果0．9%氯化钠溶液组10只小鼠9只有肿瘤转移,N-去硫酸肝素组10只小鼠只有2只转移,两组间差异有统计学意义(P＜0．05)。未发现出血等不良反应。0．9%氯化钠溶液组平均微血管密度为9．1±3．4,N-去硫酸肝素组为4．7±1．8,两组间差异有统计学意义(t=3．617,P＜0．05)。0．9%氯化钠溶液组有9只VEGF阳性表达,明显高于N-去硫酸肝素组的2只(P＜0．05)。荧光定量PCR测定显示,N-去硫酸肝素组VEGF mRNA(Ct：19．56±1．53)表达较0．9%氯化钠溶液组(Ct=16．38±1．68)低,两组间差异有统计学意义(t=4．425,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,抑制肿瘤转移。N-去硫酸肝素无明显出血等不良反应。
Objective To investigate the effects of N-desulfated heparin on tumor metastasis, angiogenesis and vascular endothelial growth factor (VEGF) in metastatic gastric cancer tissue in non-obesity diabetes (NOD) severe combined immunodeficiency (SCID) VEGF) expression. Methods Gastric metastasis model of NOD SCID mice was established in situ. The 20 mice were divided into 2 groups. One week after the transplantation, 0.9% sodium chloride solution (0.9% sodium chloride solution) and 10 mg / kg N-desulfated heparin (N-desulfated heparin) For a total of 3 weeks. The animals were sacrificed at the 6th week to observe the tumor metastasis. The microvessel density and VEGF expression in the tumor tissue were detected by immunohistochemistry. The expression of VEGF mRNA was detected by quantitative PCR. Results Nine of 10 mice in 0.9% sodium chloride solution had tumor metastasis, and only 2 of 10 mice in N-desulfated heparin group had metastasis. The difference between the two groups was statistically significant (P <0.05). No bleeding and other adverse reactions were found. The mean microvessel density in the 0.9% sodium chloride solution group was 9.1 ± 3.4 and in the N-desulfated heparin group was 4.7 ± 1.8, with a significant difference between the two groups (t = 3.617 , P <0.05). The positive expression of VEGF in 9% sodium chloride solution group was significantly higher than that in the N-desulfated heparin group (P <0.05). Fluorescence quantitative PCR showed that the expression of VEGF mRNA (Ct: 19.56 ± 1.53) in N-desulfated heparin group was lower than that in 0.9% sodium chloride solution group (Ct = 16.38 ± 1.68) The difference between the two groups was statistically significant (t = 4.425, P <0.05). Conclusion N-desulfated heparin inhibits tumor metastasis by inhibiting VEGF expression and angiogenesis in tumor tissue. N-desulfated heparin no obvious bleeding and other adverse reactions.