低氧诱导因子-1、促红细胞生成素在血管性痴呆大鼠海马的表达

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

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-1/EPO缺氧信号转导途径发挥了保护作用。

Objective To observe the expression rule of hypoxia inducible factor-1 （HIF-1α） 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-1α 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-1α 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-1α and EPO at each ischemic point and their corresponding learning-memory ability were in significant correlation at the 0.01 level. Conclusion Both HIF-1α and EPO contribute to the formation of VD, and HIF-1/EPO anoxic signal transduction may play a protecting role in this process.