摘要
目的研究慢性脑缺血大鼠海马中DNA损伤修复相关蛋白脱嘌呤／脱嘧啶核酸内切酶／氧化还原因子-1(APE／Ref-1)的活性变化与神经元的凋亡,并探讨两者之间的相关性。方法成年雄性Wistar大鼠40只,随机分为假手术组,持久性双侧颈总动脉结扎(2-VO)1周组、3周组、8周组,每组各10只,用Western blotting检测其APE蛋白表达水平的变化,并用流式细胞仪定量检测海马神经元的凋亡程度。结果 2-VO 1周组APE蛋白的表达量明显下降,与对照组相比差异有显著性(P<0．01), 随后其蛋白表达水平逐渐上升,但仍低于对照组水平(P<0．05);用流式细胞仪检测各组的凋亡率发现 2-VO 1周组、3周组凋亡率较高,与对照组相比差异有显著性(P<0．01)。结论慢性脑缺血早期DNA 修复蛋白APE活性下降,同时其神经元凋亡率较高,后期蛋白表达水平逐渐上升,神经元的凋亡程度也逐渐下降,表明DNA损伤与修复失衡所致的神经元凋亡是慢性缺血性脑损伤发病的重要机制。
Objective To investigate the activity changes of apurinic/apyrimidinic endonuclease （APE/Ref-1） protein involved in DNA repair and the neuronal apoptosis in the hippocampus of Wistar rats after chronic cerebral ischemia and to explore the relationship between them. Methods Forty male Wistar rats were equally divided into 4 groups： control group and 2-VO model groups （permanent ligation of bilateral common carotid arteries for 1, 3 and 8 weeks, respectively）. The brains were taken at week 1, 3 and 8 after the establishment of models for measuring the expression of APE protein using Western blotting, and detecting the neuronal apoptosis by flow cytometry （FCM）. Results In the 2-VO 1 week group, APE protein levels were down-regulated in the hippocampus compared to the control group （P〈0.01）, and in the 2-VO 3, 8 week groups, the protein levels were increased gradually, but still lower than that of the control group （P〈0.05）. FCM showed that the neuronal apoptosis was more obvious in 2-VO 1, 3 week groups compared with the control group （P〈0.01）. Conclusion Chronic cerebral ischemia can induce the down-regulation of DNA repair protein APE at early stage after 2-VO, at the same time the neuronal apoptosis was also obvious, while at later stage the APE protein increases and the neuronal apoptosis decreases, which suggests the failure of DNA repair function may play an important role in the neuronal apoptosis in chronic cerebral ischemia.
出处
《中华神经医学杂志》
CAS
CSCD
2006年第4期363-365,385,共4页
Chinese Journal of Neuromedicine
基金
国家自然科学基金(30270483)
