创伤性颅脑损伤后缺氧诱导因子－1α的表达及作用

摘要

目的：探索大鼠创伤性颅脑损伤（ TBI）后缺氧诱导因子－1α（ HIF－1α）的动态表达及其作用机制。方法96只雄性SD大鼠随机分为对照组、假手术组、TBI组、药物干预组。采用改良Feeney方法制作TBI模型，利用HIF－1α阻滞剂二甲基雌氧二醇（2－ME－2，2．5 mg／kg）对实验组进行药物干预；利用RT－PCR、Western blot等分子生物学技术分别观察不同时间点脯氨酸羟化酶区域蛋白2（ PHD2）、HIF－1α及血管内皮细胞生长因子（ VEGF）、Ang－1的表达情况。结果 TBI组HIF－1α表达较对照组和假手术组明显增加，HIF－1α于6 h表达开始增加，24 h～3 d达高峰，7 d后下降至正常水平，其表达增加与PHD2蛋白降解有关；2－ME－2干预后HIF－1α、VEGF、Ang－1表达较TBI组下降。结论 TBI后HIF－1α表达增加，诱导血管再生相关基因VEGF、Ang－1的表达，促进损伤血管的修复和再生。%Objective To investigate the expression of hypoxia-inducible factor-1α( HIF-1α) and its related mechanism.Methods Ninety-six Male SD rats were divided into four groups:Control group (n=8), Sham group (sham operate, n=8), traumatic brain injury group (TBI group, n=40), TBI treated with 2ME2 group (n=40).TBI model refers to Feeney's method.At the time point 6 h, 24 h, 3 d, 7 d, 14 d after modeling, RT -PCR and Western blotting analysis were respectively used to determine the expression level of PHD2/HIF -1α/VEGF/Ang -1 mRNA and protein.Results Compared with sham-operated controls, the expression of HIF-1αin TBI group has been significantly enhanced ( P <0.05 ) , which related to the degradation of PHD2 following TBI induction.HIF-1αexpression started to increase 6 h after TBI modeling; it kept an increased level within 24 h and reached to a peak 3 d after TBI;and fell to common levels seven days after TBI.While VEGF/Ang-1 expression was significant (P<0.01) decreased after inhibition of HIF-1αby 2 -ME-2.Conclusion The expression of HIF-1αincreased after experimental TBI, which can induce its downstream target gene expression to promote the repairment of injured vascular and angiogenensis.