肝素硅阿霉素抗癌药物系统对鸡胚尿囊膜血管生成的影响

Effect of doxorubicin heparinized mesoporous silica nanoparticles anticancer drug system on the angiogenesis of allantoic membrane

目的研究肝素硅阿霉素抗癌药物系统(DHN)对碱性成纤维生长因子(b-FGF)诱导血管生成的抑制作用。方法 b-FGF诱导实验分为9组:空白组,模型组(b-FGF),对照A组(介孔硅)、B组(肝素硅)、C组(肝素)、D组(阿霉素1μg),3个剂量实验组(DHN,10,5,1μg);各组b-FGF的用量均为每胚0.1μg,空白组和对照A、B、C组的给药量为10μg。新生血管实验不加b-FGF以外,其余分组与给药情况与b-FGF实验一致。新鲜受精鸡胚发育至11 d,开窗加药,3 d后取加药部位及其周围的尿囊膜,BI-2000图像分析系统下计数CAM的血管分叉数及血管内径,计算血管生成抑制率。结果 DHN各组的血管分支数及血管直径较模型组显著减小,3个剂量实验组对b-FGF诱导的CAM血管生成的抑制率分别为69.1%,61.1%,56.2%。DHN对正常新生血管的抑制率分别为41.6%,20.5%,10.6%。结论 DHN对b-FGF诱导的血管生成和正常新生血管生成均有一定的抑制作用。

1Objective To investigate the effect of doxorubicin（ Dox） heparinized mesoporous silica nanoparticles anticancer drug system（ DHN）on bovine basic fibroblast growth factor（ b-FGF）-induced angiogenesis of chorioallantoic membrane（ CAM）. Methods In the experiment of b-FGF-induced angiogenesis,the mice were divided in blank group（ 10 μg sailine）,model group（ b-FGF）,control group-A（ 10 μg MSNs）,control group-B（ 10 μg HMSN）,control group-C（ 10 μg Heparin）,control group-D（ 1 μg Dox）,different dose DHN group（ 10,5,1 μg DHN）,0. 1 μg b-FGF was given in each group except blank group. In the experiment of normal angiogenesis（ without b-FGF）,the grouping and the dose were same as groups in the b-FGF-induced angiogenesis study. After incubation at 37 ℃ for 11 days,fertilized eggs were opened and the shell membranes were taken off. Then,the agents in PBS were applied to the top of chorioallantoic membrane,once daily for 3 d. Finally,the chorioallantoic membranes were taken off and fixed. The tube formation of CAM was monitored and the numbers and internal diameters of the blood vessels were observed and statistical analysis by BI-2000 photograph system. Results The number of blood vessels and vascular diameter of CAM were significantly decreased inDHN group compared with model group. High,medium and low doses of DHN inhibited b-FGF-induced CAM angiogenesis in a dose-dependent manner,the inhibitory rate was 69. 1 %,61. 1 %,56. 2 %,respectively.DHN also inhibited the formation of new blood vessels of CAM without b-FGF treatment,the inhibition rate were41. 6 %,20. 5 %,10. 6 %. Conclusion DHN may inhibit b-FGF-induced angiogenesis and the formation of new blood vessels of CAM.