兔颈动脉粥样硬化早期斑块内HIF-1α与新生血管的关系

HIF-1α and neovascularization in early carotid atherosclerosis plaques in rabbits

目的:通过建立颈动脉粥样硬化(CAS)模型来探讨早期斑块内缺氧诱导因子-1α(HIF-1α)与新生血管形成的关系;研究超声造影(CEUS)能否检测早期斑块内新生血管的变化。方法:采取高脂饮食联合硅橡胶圈干预建立兔CAS模型。第14,28天行CEUS检测CAS斑块内新生血管形成,通过时间-强度曲线得出斑块内的造影剂峰值强度(PI)并进行前后对比分析。通过免疫组织化学检测斑块内CD31,HIF-1α,VEGF,α-actin,RAM-11的表达,进行组间比较及相关性分析。同时对PI与CD31进行相关性分析。结果:第14天CEUS显示CAS斑块内已有新生血管形成;第14,28天斑块内PI差异有统计学意义(P<0.01)。CAS斑块内HIF-1α,VEGF,RAM-11,α-actin,CD31第14,28天表达差异具有统计学意义(P<0.01)。CAS斑块内HIF-1α分别与VEGF,RAM-11,α-actin,CD31表达呈正相关;PI与CD31表达亦呈正相关。结论:在CAS演变过程中,早期斑块内即有新生血管形成,HIF-1α在CAS早期病变中促进新生血管形成。CEUS能检测CAS早期斑块内新生血管形成及其变化。

Objective To explore the relationship between hypoxia-inducible foctor-1α （HIF-1α） and neovascularization in early atherosclerosis plaques by establishing rabbit carotid atherosclerosis models,and to observe the value of contrast-enhanced ultrasound in the detection of neovascularization. Methods We provided high-fat diet combined with the implantation of silicone rubber ring to establish carotid atherosclerosis in rat models. On the 14th and 28th days,we detected neovascularization in the carotid atherosclerotic plaques by contrast-enhanced ultrasound,obtained the peak intensity （PI） of the contrast agent in the plaques by time-intensity curve （TIC） and analyzed the difference. We also tested the level of HIF-1α,vascular endothelial growth factor （VEGF）,cluster of differentiation 31 （CD31）,α-actin,and RAM-11 by immunohistochemical method in each group,analyzed their correlation,and the correlation between PI and CD31 expression. Results On the 14th day,contrast-enhanced ultrasound showed the neovascularization in the carotid atherosclerotic plaques. On the 14th and 28th days,the intensity of contrast-enhanced ultrasound showed significant difference,the mean optical density of HIF-1α,VEGF,CD31,RAM-11,and α-actin within the carotid atherosclerotic plaques also showed statistical difference. The expressions between HIF-1α and VEGF,HIF-1α and CD31,HIF-1α and RAM-11,HIF-1α and α-actin,as well as PI and CD31 showed highly positive correlations.Conclusion During the process of atherosclerosis evolution,neovascularization in the atherosclerotic plaques has come into being in the early period,and HIF-1α in early atherosclerosis can promote the formation of neovascularization. Contrast-enhanced ultrasound can detect the dynamic changes of neovascularization within early atherosclerotic plaques.