血管生成素对糖尿病大鼠股骨头血管新生及渗漏的影响

The effects of Ang-1 on the angiogenesis and vascular leakage of diabetic rats' femoral head

目的探讨血管生成素1(angi.Poietin-1,Ang-1)对糖尿病大鼠股骨头微血管新生及渗漏的影响。方法建立速发型链脲佐菌素(streptozotocin,STZ)糖尿病大鼠模型,随机分为正常5周组(CON1)、10周组(CON2)及15周组(CON3),糖尿病5周组(DM1)、10周组(DM2)及15周组(DM3),每组10只。墨汁灌注观测股骨头微血管密度;摘取模型动物股骨头组织,免疫组化分析凝血因子Ⅷ(FⅧ)表达;原位杂交分析血管内皮生长因子(VEGFmRNA)表达强度;RT-PCR分析Ang-1的mRNA表达。结果糖尿病大鼠股骨头随病程发展,Ang-1、FⅧ因子表达上升,与正常组相比有显著性差异(P<0.01)。VEGFmRNA表达量均高于正常组(P<0.01);微血管密度加大,显示血管增生、渗漏。结论糖尿病股骨头Ang-1与VEGFmRNA相互协同或拮抗分别促进微血管增生、抗血管渗漏。表达于血管内皮细胞的FⅧ及VEGFmRNA与微血管密度(MVD)变化存在正相关。

Objective To probe into the effects of Ang-1 on the angiogenesis and microvascular leakage of diabetic rats＇ femoral head.Methods By establishing models of the rats with STZ diabetes,and randomly dividing them into the normal groups（CON1,CON2 and CON3） and the diabetic groups（DM1,DM2 and DM3） with 10 rats each group,the microvascular density through infusion with ink,the expression of blood coagulation factorⅧ with immunohistochemistry,and the expression of the mRNA of both VEGF by hybridization in situ and Ang-1 by RT-PCR,were performed.Results The diabetic rats＇femoral head varied in the course of illness.Their expression of Ang-1,blood coagulation factorⅧ,and VEGF mRNA significantly rose,as compared with those of rats in the normal groups（P0.01）.The microvascular density enlarged with vascular proliferation and leakage.Conclusions The interaction and antagonism between Ang-1 and VEGF mRNA of diabetic rats＇ femoral head can promote microvascular proliferation and resist vascular leakage.The mRNA expression of both coagulation factorⅧ and VEGF in vascular endothelial cells have a positive correlation with the changes of their microvascular density.