缺氧诱导因子-1α在脑出血早期脑水肿形成中的作用

目的:探讨高血压性脑出血患者血肿周围脑组织缺氧诱导因子-1α(HIF-1α)在早期脑水肿形成中的作用和机制.方法:血肿清除术治疗的32例高血压性脑出血患者血肿周围脑组织,采用免疫组织化学染色技术测定HIF-1α和血管内皮生长因子(VEGF)的表达;根据术前头颅CT测量血肿周围脑水肿体积;采用双盲法对染色结果和脑水肿体积进行分析.结果:出血4h可见神经元和血管内皮细胞肿胀,血肿周围脑组织可见散在的HIF-1α阳性神经元,出血24～48h时HIF-1α表达达高峰,49～72h持续高表达,与正常脑组织相比存在显著差异(P＜0.01).HIF-1α表达与VEGF表达(r=0.72,t=6.37,P＜0.01)和脑水肿体积(r=0.64,t=4.56,P＜0.01)呈正相关.结论:高血压脑出血血肿周围脑组织HIF-1α表达与早期脑水肿形成有关,HIF-1α可能通过诱导和调控VEGF表达促进脑水肿形成.

Effect of Hypoxia-Inducible Factor-1α on Early Formation of Brain Edema During Intracerebral Hemorrhage

Objective:To investigate the effect and mechanism of hypoxia-inducible factor-1α (HIF-1α)in perihematomal brain tissue on the early formation of edema in patients with hyper-tensive intracerebral hemorrhage.Methods:The perihematomal brain tissue in 32 patients with hypertensive intracerebral hemorrhage were treated with hematoma evacuation.The expressions of HIF-1α and vascular endothelial growth factor(VEGF)were measured by immunohistochem- istry staining technique.The volume of perihematomal edema was determined on the basis of reoperative head CT scan.The results of staining and the volume of edema were analyzed by using double-blind method.Resets:Neuron and vascular endothelial cell swelling were observed 4 hours after cerebral hemorrhage,and the scattered HIF-1α positive neurons were visible.The expressions of HIF-1α reached the peak(at 24 to 48 hours,and went on high expressions at 49 to 72 hours.There was significant difference as compared with the normal brain tissue(P＜0.01). There were positive correlations between the expressions of HIF-1α and VEGF (r=0.72,t=6.37,P＜0.01)and the volume of brain edema(r=0.64,t=4.56,P＜0.01).Conclusions: The expression of HIF-1α in perihematomal brain tissue of hypertensive cerebral hemorrhage iS associated with the early formation of cerebral edema.HIF-1α may accelerate the formation of brain edema by inducing and regulating the expression of VEGF.