缺氧诱导因子-1α(HIF-1α)在动脉粥样硬化斑块中的表达及血管生成关系

目的:观察缺氧诱导因子-1α(HIF-1α)在动脉粥样硬化(As)斑块中的表达,探讨HIF-1α与斑块血管生成的关系。方法:24只Wistar大鼠随机分为正常组8只(普通饲料)和As模型组16只(高脂饮食+VitD3)。实验3个月后,检测血清总胆固醇(TC)、甘油三脂(TG);取主动脉石蜡包埋切片,HE染色;测量主动脉斑块占内膜总面积比(RAAPIs),内膜中膜面积比(I/M);免疫组化SP法检测HIF-1α蛋白的表达情况,鼠单克隆抗体CD34计数新生血管数目(MVD)。结果:实验后模型组血清TC、TG水平较正常组明显升高[(3.30±0.35)vs(1.51±0.19);(0.85±0.12)vs(0.50±0.14)],差异有统计学意义(P<0.01);模型组中RAAPIs,I/M明显高于正常组(P<0.05);模型组中HIF-1α蛋白表达增高;正常组中HIF-1α未见表达(87.5%vs 0%,P<0.01);模型组中微血管密度(MVD)明显高于正常组[(13.14±2.45)vs 0,P<0.05];不稳定斑块组HIF-1α、MVD均高于稳定斑块组[(100%vs 66.6%),(14.30±1.70)vs(10.25±1.26),P<0.05)],HIF-1α蛋白表达与MVD表达呈正相关(r=0.704,P=0.005)。结论:HIF-1α可通过促进As斑块内血管生成,从而增加斑块的不稳定性;HIF-1α的含量可能是影响斑块稳定性的重要因素。

The expression of hypoxia-inducible factor-1α and in atherosclerosis and the relationship with neovascularization

Objective:To analyze the expression of hypoxia-inducible factor-1α and the relationship between HIF-1α and neovascularization in atherosclerotic plaque.Method:24 Wistar mouse was divided randomly into two groups: the normal group and the model group,to establish the atherosclerosis model with high lipid +vitamin D_3 in the model group.Serum lipid was derermined.immunohistochemical staining method was used to show the expression of HIF-1α and micro-vessel density.Result:The level of serum total cholesterol(TC) and triglyceride(TG) in model group were higher than normal one[(3.30±0.35) vs(1.51±0.19);(0.85±0.12) vs(0.50±0.14),P<0.01].The expression of HIF-1α(87.5%vs 0%,P<0.01) and MVD in model group were higher than the normal one(13.14±2.45 vs 0,P<0.05),which was the same between unstable group and stable one[100% vs 66.6%,(14.30±1.70) vs(10.25±1.26),P<0.05].Positive correlation was found between HIF-1α and MVD(r=0.704,P=0.005).Conclusion:The content of HIF-1α may be the factor of stabilization of plaque,HIF-1α can induce the form of neovascularization in atherosclerotic plaque,and promt the instabilization of plaque.