缺氧诱导因子-1α及其相关基因在腹主动脉瘤中的表达及意义

The expression and significance of hypoxia-inducible factor-la and related genes in abdominal aorta aneurysm

目的研究缺氧诱导因子(HIF)-1α信号转导通路及其相关基因在腹主动脉瘤(AAA)中的表达,探讨AAA的发病机制。方法选取AAA标本22例,以5例腹主动脉(NA)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-1α的mRNA及蛋白产物表达,Western蛋白印迹或免疫组织化学方法检测血管内皮生长因子(VEGF)及半胱氨酸蛋白酶(caspase)-3的表达,免疫组织化学抗CD34染色法检测微血管密度(MVD)。结果 AAA组织中HIF-1α的mRNA及蛋白产物表达明显高于NA(P<0.01);caspase-3和VEGF表达亦明显增强(P<0.01),与HIF-1α表达呈显著正相关(r值分别为0.783和0.693,P<0.01)。HIF-1α表达主要分布在AAA中层血管平滑肌细胞及外膜处,与caspase-3和VEGF的分布部位基本一致。AAA中微血管密度明显增加(P<0.01))。结论HIF-1α在AAA疾病进展过程中可能发挥重要作用,其作用机制可能是通过调控VEGF或caspase-3的表达而实现的。

Objective To study the expression of hypoxia-inducible factor( HIF)-1α and related genes in abdominal aorta aneurysm ( AAA) and explore the underlying pathogenesis. Methods Twenty-two AAA specimens were collected and 5 normal abdominal aorta tissue were used as control. Northern blot, western blot and immunohistochemistry were used to evaluated the expression of HIF-1α mRNA and protein product. Western blot and immunohistochemistry method were also used to determine the expression of vascular endothelial growth factor ( VEGF) and caspase-3. Microvessel density ( MVD) was studied by immunohistochemistry stain of CD34. Results The expression of HIF-lα mRNA and protein product were significantly higher in AAA than that in normal abdominal aorta (P < 0. 01). The expression of VEGF and caspase-3 were also higher in AAA and both had a significantly positive relationship with HIF-1 α expression (P < 0. 01 ). Most of the positive cells located in VSMC and adventitia of AAA. The MVD counts were higher in AAA. Conclusion HIF-1 α may have an important role the development of AAA, which maybe obtained by regulating the expression of VEGF or caspase-3.