慢性脑缺血大鼠海马中APE、PCNA的表达与神经细胞凋亡  

Apurinic/apyrimidinic endonuclease,proliferating cell nuclear antigen protein expression and the neuronal apoptosis in rat hippocampus induced by chronic cerebral ischemia

作　　者：余芬[1] 袁秀珠[1] 

机构地区：[1]武汉大学附属同仁医院,武汉430060

出　　处：《山东医药》2009年第33期1-4,共4页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(30270483)

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(APE)、增生细胞核抗原(PCNA)的活性变化及神经元的凋亡情况,并探讨三者之间的相关性。方法成年雄性W istar大鼠随机均分为假手术组、持久性双侧颈总动脉结扎(2-VO)1周组、3周组、8周组,用W estern b lotting检测各组海马组织中APE、PCNA蛋白表达水平,用流式细胞仪检测海马神经元的凋亡程度。结果2-VO 1周组APE、PCNA蛋白的表达量明显低于对照组(P<0.01),随着2-VO时间的延长其蛋白表达水平逐渐上升,但仍低于对照组(P<0.05);慢性脑缺氧大鼠术后1周时海马神经细胞凋亡百分率最高为22.66%,以后随时间的延长细胞凋亡数逐渐下降(P<0.01)。结论慢性脑缺血大鼠早期APE、PCNA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细胞凋亡是慢性缺血性脑损伤发病的重要机制之一。Objective To investigate the protein expressions of apurinie/apyrimidinie endonuelease（APE） ,proliferating cell nuclear antigen （PCNA） and the neuronal apoptosis in the hippocampus of Wistar rats with chronic cerebral ischemia. Methods Male Wistar rats were divided into 4 groups：control group, 2-vessel occlusion（VO） for one-week group,2- VO for three-week group and 2-VO for elght-week group. The expressions of APE, PCNA protein in the hippocampus were measured using Western Blotting, and the neuronal apoptosis was detected by flow cytometry（FCM）. Results The levels of APE, PCNA protein in the 2-VO for one-week group were lower than those of the control group（ aU P 〈 0.01 ）. Compared with the 2-VO for one-week group, the 2-VO for three-week and eight-week groups showed the protein levels of APE and PCNA increased gradually. The levels of APE, PCNA protein in the 2-VO for three-week and eight-week groups were lower than those of the control group（ all P 〈 0.05）. FCM showed that the neuronal apoptosis was most obvious in the the 2-VO for one-week group （22.66%）, and in the 2-VO for three-week and eight-week groups, the neuronal apoptosis was de- creased gradually（ P 〈0.01 ）. Conclusions Chronic cerebral isehemia can induce down-regulate of the protein levels of APE and PCNA at early stage after 2-VO, at the same time the neuronal apoptosis was obvious. Failure of DNA-repairing function may play an important role in the neuronal apoptosis of chronic cerebral ischemia.

关 键 词：脑缺血 DNA连接酶类 脱嘌呤/脱嘧啶核酸内切酶 增殖细胞核抗原 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学] R734.2[医药卫生—中医学]