低氧诱导因子-1α、促红细胞生成素在血管性痴呆大鼠海马的表达

目的 观察低氧诱导因子-1α（HIF-1α）和促红细胞生成素（EPO）在大鼠血管性痴呆（VD）形成过程中的动态表达规律，探讨VD发生的可能机制。方法 采用大鼠双侧颈总动脉永久性阻断法（2-VO）建立VD动物模型，应用Y型水迷宫实验测定动物的学习记忆能力，采用免疫组化法检测大鼠海马CA1区HIF-1α和EPO蛋白的表达．结果 ①随缺血时间的延长，痴呆组大鼠学习记忆能力进行性下降（P〈0．05）；②痴呆组大鼠海马CA1区HIF-1α、EPO的表达于缺血1周时最明显，此后缓慢下降，但与假手术组比较仍处于较高水平（P〈0．01）；③痴呆组大鼠两蛋白表达与学习记忆能力呈高度正相关（P〈0．01）。结论 HIF-1α和EPO参与了VD的发生发展过程，并可能在此过程中通过HIF—UEPO缺氧信号转导途径发挥了保护作用。

A Study on Expression of HIF-1α and EPO in the Hippocampus of Rats with Vascular Dementia

OBJECTIVE: To observe the expression rule of hypoxia inducible factor-1 (HIF-1alpha) and erythropoietion (EPO) in the formation of vascular dementia (VD) and investigate the possible pathogenesis of VD. METHODS: Rats of experimental group were treated with a permanent bilateral common carotid arteries (CCA) occlusion (2-VO) for establishing vascular dementia model. Rats were evaluated on learning-memory ability by Y-type water maze test. The dynamic expression of HIF-1alpha and EPO in hippocampal CA1 region were measured by immunohistochemical assay method. RESULTS: (1) The learning-memory ability of rats in VD groups was progressively decreased as the ischemic duration prolonged (P < 0.05); (2) In VD group, the expression of HIF-1alpha and EPO in hippocampal CA1 region were most obvious at 1 w, and then declined progressively but still above the normal level (P < 0.01); (3) In VD group, the expression of HIF-1alpha and EPO at each ischemic point and their corresponding learning-memory ability were in significant correlation at the 0.01 level. CONCLUSION: Both HIF-1alpha and EPO contribute to the formation of VD, and HIF-1/EPO anoxic signal transduction may play a protecting role in this process.