EPO对全脑缺血后低氧诱导因子1α及存活素表达的调节  

EFFECT OF ERYTHROPOIETIN ON HIF-1α、SURVIVIN FOLLOWING GLOBAL CEREBRAL ISCHEMIA IN RATS

作　　者：欧阳和中[1] 李云[2] 

机构地区：[1]江苏省丹阳市人民医院神经内科,丹阳212300 [2]山东省济南市中心医院急诊科,济南250013

出　　处：《中国科技信息》2011年第4期208-211,共4页China Science and Technology Information

摘　　要：[目的]研究促红细胞生成素对全脑缺血再灌注大鼠缺氧诱导因子1α和凋亡相关蛋白存活素的调节,探讨其抗凋亡的可能机制。[方法]将成年雄性SD大鼠75只按随机数字表法分为全脑缺血组(n=35)和全脑缺血EPO干预组(n=35),然后按再灌注时间不同又分为6h、12h、24h、48h、72h、5d和7d七个亚组。采用改良的Pu刘lsineli 4-VO法制作全脑缺血大鼠模型。应用TUNEL染色检测再灌注后不同时间点海马CA1区的神经元凋亡水平,免疫组织化学方法检测再灌注后不同时间点海马CA1区缺氧诱导因子1α和存活素表达水平的变化。[结果]全脑缺血EPO干预组24h至7d亚组TUNEL阳性神经元计数分别为1.50±0.73、3.14±0.88、5.78±1.03、7.78±1.79、10.34±1.82.与全脑缺血组相应时间点亚组相比明显减少,差异均有统计学意义(P<0.05)。全脑缺血EPO干预组48h至5d亚组HIF-1α表达阳性细胞计数分别为11.26±0.02、20.28±2.03、3.33±0.04,与全脑缺血组相应时间点亚组相比明显减少,差异均有统计学意义(P<0.05).全脑缺血EPO干预组24h至5d亚组survivin蛋白表达阳性细胞计数分别为12.21±1.04、16.34±4.02、24.33±3.03、30.52±5.04,与全脑缺血组相应时间点亚组相比明显增高,差异均有统计学意义(P<0.05)。[结论]在全脑缺血急性期,EPO抑制HIF-1α的表达而使存活素表达升高,具有一定的神经保护作用.Objective To observe the effects of EPO on the Hif-1α、survivin expression after global cerebral ischemia-reperfusion in rats,exploring its antiapoptosis mechanisms.Methods The experimental GI model was established by 4-vessel occlusion method and confirmed successfully by an electroencephalogram（EEG）.Seventy-nine adult male Sprague–Dawley rats were randomly divided into sham group（n=5）,global cerebral ischemia group（GI,n=35） and global cerebral ischemia ＋ EPO treatment group（GI＋EPO,n=35）,and the two latter groups to seven subsets each with 5 rats.EPO were administered to rats in GI＋EPO group by abdominal cavity injection（4000u/ kg /day） one time a day with the same dosage in the first 3 days.The cerebral hippocampus tissues were obtained 3 days after sham operation in sham group and 6、12 hours、1、2、3、5 and 7 days after reperfusion in the GI and GI ＋EPO groups for determining apoptosis of cells by TUNEL and the expressions of Hif-1α、survivin proteins by Immunohistochemistry staining method.All the data in this study were expressed as mean±standard deviation（SD）.A value of P〈0.05 was considered statistically significant.Results TUNEL staining Compared to the sham group,the number of apoptotic cells in subset 1、2、3、5、7d of GI group and subset 2、3、5、7d of GI＋EPO group were significantly increased.The number of apoptotic cells in subset 1、2、3、5、7d of GI＋EPO group were significantly less than of GI group.Immunohistochemistry stainingExpression of Hif-1αCompared to the sham group Hif-1αimmunopositive cells were significantly increased in the injured hippocampus in 1、2、3、5、7 d subsets of GI group（P〈0.01） and GI＋EPO group.Compared to the corresponding subsets of GI group,expression level of survivin in subsets 1、2、3、5d of GI＋EPO were significantly higher.Expression of survivinCompared to the sham group survivin immunopositive cells were significantly increased in the injured hippocampus in 3、 5、7 d subsets of GI gro

关 键 词：全脑缺血再灌注 海马 存活素 促红细胞生成素 缺氧诱导因子-1α 

分 类 号：R743[医药卫生—神经病学与精神病学]