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染料木素对卵巢切除大鼠学习记忆能力的影响
引用本文:李骅,王剑波,王四旺.染料木素对卵巢切除大鼠学习记忆能力的影响[J].生物磁学,2009(20):3826-3830.
作者姓名:李骅  王剑波  王四旺
作者单位:第四军医大学药学系药物研究所,陕西西安710032
基金项目:基金项目:陕西省社会发展攻关计划项目(2005K14.G3-3)染料木素已获中国SFDA临床研究批件(2004L01547)
摘    要:目的:探讨染料木素对卵巢切除大鼠学习记忆能力的影响及作用机制。方法:将40只SD雌性大鼠随机分为用假手术组、去卵巢对照组、染料木素高剂量、低剂量组、17β-雌二醇组,切除卵巢建立学习和记忆能力受损的模型。灌胃给药6周后Morris水迷宫测定各组大鼠学习记忆能力,免疫组化法观察大鼠海马微管相关蛋白(tau蛋白)阳性表达情况,测定大鼠脑组织中乙酰胆碱酯酶(AchE)、乙酰胆碱转移酶(ChaT)、超氧化物歧化酶(SOD)的活性及丙二醛(MDA)的含量,观察海马组织超微结构变化。结果:大鼠切除卵巢后Morris水迷宫测定的学习记忆能力显著下降,微管相关蛋白(tau蛋白)异常磷酸化阳性表达率增高,前脑皮质中超氧化物歧化酶(SOD)、乙酰胆碱转移酶(ChaT)活性降低,丙二醛(MDA)含量、乙酰胆碱酯酶(AchE)活性增高。低剂量的染料木素可以发挥类雌激素样作用,改善去卵巢大鼠的以上症状。结论:染料木素对卵巢切除导致的学习和记忆能力下降有改善作用,低剂量效果显著,其可能的机制是:抑制了脑内AchE的活性,使乙酰胆碱的降解减少;增强脑组织抗氧化能力;稳定微管相关蛋白(tau蛋白),降低tau蛋白异常磷酸化水平。

关 键 词:植物雌激素  染料木素  去势大鼠  学习记忆能力

Effect of genistein on learning and memory in ovariectomized rats
LI Hua,WANG Jian-bo,WANG Si-wang.Effect of genistein on learning and memory in ovariectomized rats[J].Biomagnetism,2009(20):3826-3830.
Authors:LI Hua  WANG Jian-bo  WANG Si-wang
Institution:(Institute of Materia Medica, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, China)
Abstract:Objective: To evaluate the effect of genistein on learning and memory in ovariectomized (OVX) Sprague Dawley(SD) rats and their mechanism of action. Methods: Forty female SD rats were randomized into mimic sham operation group (Sham), ovariectomized group (OVX), OVX + high-dose Genistein group(G-h),OVX + low-dose Genistein group(G-l) and 17β-estradiol group (L).These rats were intragastric administrated (ig) with drugs or distilled water for six weeks respectively. Learning and memory were tested by Morris water maze. The hyperphosphorylation of tau protein was detected by immunohistochemical staining and the results compared. AchE, ChaT, SOD activity and MDA contents were assayed in frontal cortex.The ultrastructural changes of the hippocampus was observed by electron microscope. Results: Six weeks after Ovariectomy (OVX) resulted in the decrease on learning and memory in female rats tested by Morris water maze. The hyperphosphorylate tau protein positive cell in hippocampus saw more expression. The SOD, ChaT activities in frontal cortex were found decrease while the MDA content, AchE activity were found increased. After treatment of low-dose-Genistein and 17β-estradiol, learning and memory was improved markedly. Conclusion: Low dose and 17β-estradiol can ameliorate the reduction of learning and memory in ovariectomized rats, which may correlate with the decrease of the Ache activity, the increase of the ChaT activity, the enhancement of anti-oxidation ability and the inhibition of abnormal phosphorylation of tau in the hippocampus.
Keywords:Phytoestrogens  Genistein  Ovariectomized(OVX)rat  Learning and memory
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