雌激素对大鼠空间记忆功能的影响及其可能机制  

Effects of estrogen on rat spatial memory ability and the possible mechanism

作　　者：杨红旗[1,2] 李学[1,2] 孙治坤[1,2] 蒋秋焕[1,2] 尚茜[1,2] 王文霞[1,2] 马建军[1,2] 

机构地区：[1]河南省人民医院 [2]郑州大学人民医院神经内科,450000

出　　处：《中华脑科疾病与康复杂志（电子版）》2013年第3期27-30,共4页Chinese Journal of Brain Diseases and Rehabilitation（Electronic Edition）

基　　金：河南省重点科技攻关计划项目(112102310684);河南省医学科技公关计划项目(201203130)

摘　　要：目的利用去势大鼠研究雌激素对大鼠空间记忆功能的影响及其可能机制。方法切除大鼠双侧卵巢制作雌激素缺失模型(Ovx),连续腹腔注射东莨菪碱模拟痴呆,然后给予17β-雌二醇补充治疗(Ovx+E2)。利用水迷宫测定各组大鼠逃避潜伏期;Western印迹检测大鼠海马脑源性神经营养因子(BDNF)表达和糖原合成激酶-3β(GSK-3β)的磷酸化,放射免疫法测定GSK活性。结果 Ovx大鼠血液雌激素水平[(11.6±4.5)pg/ml]明显低于对照组[(23.4±10.7)pg/ml,q=8.217,P=0.003],而给予17β-雌二醇替代治疗后雌激素水平较Ovx大鼠显著上升[(67.3±15.2)pg/ml,q=7.069,P=0.001]。Ovx大鼠的水迷宫逃避潜伏期[(76.6±23.4)s]较对照组[(26.5±13.6)s]显著延长(q=9.365,P=0.004),而给予17β-雌二醇补充治疗后逃避潜伏期[(45.8±17.6)s,q=17.534,P=0.003]降低。Ovx大鼠海马的BDNF表达[(64.3±10.8)%]较对照组[(100.0±10.6)%]显著降低(q=10.802,P=0.007),17β-雌二醇补充治疗后BDNF表达上调[(92.5±12.7)%,q=7.160,P=0.03]。Ovx大鼠海马的GSK-3β磷酸化[(58.6±11.4)%]较对照组下降[(100.0±12.2)%,q=8.063,P=0.02],GSK活性[(167.3±18.5)%]较对照组增加[(100.0±14.6)%,q=7.316,P=0.008];17β-雌二醇补充治疗后GSK-3β磷酸化增加[(92.5±10.4)%,q=6.308,P=0.036],GSK活性较Ovx大鼠[(112.3±12.8)%,q=11.305,P=0.003]降低。结论去势大鼠腹腔注射东莨菪碱成功的模拟了痴呆模型;去势后雌激素替代治疗能改善痴呆大鼠的空间记忆能力,可能与提高BDNF表达和GSK-3β磷酸化及抑制GSK活性有关。Objective To investigate the effects of estrogen on rat spatial memory ability in ovarieetomy rats. Methods Female rat ovaries were ectomized to mimic estrogen-depletion models and then 17β-estradiol was administered by powdering the hormone into the soy-free chow as a way of replacement therapy. Dementia rats were made by successive intraperitoneal injection of scopolamine and water-maze test were performed to measure escape latency in each group. Hippocampus brain-derived neurotrophic factor （BDNF） expression and glycogen synthase kinase-3B（GSK-3β） phosphorylation were detected by Western Blot analysis and GSK activity were detected by radioimmunoassays. Results Ovariectomy significantly decreased serum estrogen level[ （ 11.6 ± 4. 5 ） pg/ml, q = 8. 217, P = 0. 003 ] as compared with control group [ （23.4 ± 10. 7 ） pg/ml ], while 17 β -estradiol replacement therapy increased the estrogen level [ （ 67. 3 ± 15.2） pg/ml, q = 7.069, P = 0. 001 ] in blood. Ovariectomy significantly increased escape latency [ （76. 6 ± 23.4） s ] as compared with control group [ （26.5±13.6 ） s, q = 9. 365, P = 0. 004 ], while 1713-estradiol replacement decreased escape latency [ （ 45.8 ± 17. 6 ） s, q = 17. 534, P =0. 003 ] as compared with ovariectomy group. Ovariectomy significantly decreased hippocampus BDNF expression （ q = 10. 802, P = 0. 007 ） and GSK-3β phosphorylation （ q = 8. 063, P = O. 02 ）, but increased GSK activity （ q = 7. 316, P =0. 008）as compared with control group, while 17β-estradiol administration partially reverses these effects. Conclusion Dementia rats were successfully induced in ovarieetomy rats by intraperitoneal injection of scopolamine. Estrogen replacement therapy significantly improved spatial memory ability in dementiaed rats as indicated by decreasing escape latency in water-maze test. This may be related with increased BDNF expression, GSK-3 β phosphorylation and decreased GSK activity.

关 键 词：雌激素类 阿尔茨海默病 水迷宫 

分 类 号：R363[医药卫生—病理学]