目的研究缺氧诱导因子(hypoxia—inducible factor-1α,HIF-1α)信号转导通路在破裂性腹主动脉瘤(ruptured abdominal aorta aneurysm,RAAA)中的表达,探讨AAA破裂的分子基础。方法选取RAAA标本18例,以20例AAA标本作对照。采用Northern杂交、Western蛋白印迹及免疫组织化学方法检测HIF-1仅的mRNA及蛋白产物表达,Western蛋白印迹和免疫组织化学方法检测血管内皮生长因子(VEGF)的表达,免疫组织化学抗CD34染色法检测微血管密度(microvessel density,MVD)。结果RAAA组织中HIF-1αmRNA表达明显高于AAA组(P〈0.01),免疫组化染色表明HIF-1α阳性细胞百分率为(40.9±10.8)%,与AAA(17.6±5.2)%比较差异有统计学意义(P〈0.01);VEGF表达亦明显增强(P〈0.01),与HIF-1α表达呈显著正相关(r值为0.725,P〈0.01)。HIF-1α阳性表达主要分布在AAA中层平滑肌细胞及外膜。RAAA中微血管密度明显增多(P〈0.01)。结论HIF-1α及其相关基因过表达在RAAA的分子机制中可能发挥重要作用。
Objective To study the expression of hypoxia-indueible factor( HIF)-1α and related genes in ruptured abdominal aorta aneurysm (RAAA) and explore the underlying pathogenesis. Methods 18 RAAA specimens were collected and 20 AAA tissues were used as control. Total RNA was extracted and Northern blot was used to evaluate the expression of HIF-1α mRNA. Western blot and immunohistochemistry method were used to determine the expression of HIF-1α and vascular endothelial growth factor(VEGF). Microvessel density(MVD) was measured for CD34. Results The expression of HIF-1α mRNA was significantly higher in RAAA than that in AAA ( P 〈0. 01 ). The percentage of HIF-1α positive cells detected by immunohistochemistry was (40. 9 ± 10. 8 ) %, compared with 17.6% ± 5.2% in AAA cases (P 〈 0. 01 ). The expression of VEGF was higher in RAAA and had a significantly positive relationship with HIF-1α (r = 0. 725, P 〈 0. 01 ). Most positive cells located in VSMC and adventitia of AAA. The MVD counts were higher in RAAA. Conclusion HIF-1α may have a important role in the pathogenesis of RAAA.