大鼠脑缺血后APE/Ref-1蛋白表达对神经元凋亡的影响

目的 探讨脑缺血后无嘌呤／无嘧啶核酸内切酶／氧化还原因子1（APE／Ref－1）蛋白表达变化与神经元凋亡之间的关系。方法 采用双侧颈总动脉阻断＋全身低血压法建立大鼠脑缺血模型。动物分假手术组、手术后存活1，2，3d组。用免疫组织化学方法分析各组APE／Ref-1蛋白的表达；用TUNEL染色观察脑缺血后海马CA1区神经元凋亡的情况。结果 免疫组织化学显示假手术组神经元广泛表达APE／Ref-1蛋白。在脑缺血10min后第1天海马CA1区APE／Ref-1阳性细胞开始减少，第2天明显减少。该区TUNEL阳性细胞在缺血第2天出现，第3天表现明显。APE／Ref-1和TUNEL双重染色提示丧失了APE／Ref-1免疫活性的细胞转变为TUNEL阳性细胞。结论 短暂性脑缺血后海马CA1区神经元表达APE／Ref-1蛋白减少，这种变化早于神经元凋亡，提示APE／Ref-1蛋白减少和DNA修复功能下降可能与短暂性脑缺血后发生神经元凋亡有关。

Relation of Apurinic/apyrimidinic Endonuclease Redox Factor 1 Expression and Neuronal Apoptosis after Global Cerebral Ischemia in Rats

Objective\ To explore the relationship between apurinic/apyrimidinic endonuclease/redox factor 1(APE/Ref\|1) and neuronal apoptosis after transient global cerebral ischemia in rats.\ \{Methods\}\ Global ischemia was induced by bilateral common carotid artery occlusion and hypotension.\ Expression of the APE/Ref\|1 protein was evaluated by immunohistochemical analysis.\ Apoptosis after global ischemia was observed by TUNEL staining.\ Results\ Immunohistochemistry showed the nuclear expression of APE/Ref\|1 in the control brains. Nuclear immunoreactivity of APE/Ref\|1 start decreased at 1 day and significantly decreased at 2 days in the hippocampal CA1 subregion after transient global ischemia.\ The TUNEL positive neurons were observed at 2 days and significantly at 3 days.\ Double staining with APE/Ref\|1 and TUNEL clearly showed that the neurons which lost APE/Ref\|1 immunoreactivity became TUNEL positive.\ Conclusion\ APE/Ref\|1 decreased in hippocampal CA1 neurons after transient global ischemia and this reduction induced apoptosis.\ The decrease of APE/Ref\|1 activity and the failure of DNA repair may involve the mechanism of apoptosis after transient global ischemia.