【作者】 董爱梅；

【导师】 邹莉波；

【作者基本信息】 沈阳药科大学 ， 药理学， 2003， 硕士

【摘要】 本文主要对葛根总黄酮（PIF）的抗脑血管性痴呆作用及作用机制进行了研究，同时对其有效成分之一大豆苷元（DZ）的学习记忆改善作用进行了初步的探讨。实验结果表明在反复脑缺血再灌致小鼠记忆障碍的实验中，PIF显著减少跳台实验和避暗实验中小鼠测试阶段的错误次数；在颈总动脉不完全结扎致小鼠记忆障碍的实验中，PIF能够显著减少跳台实验和避暗实验中小鼠测试阶段的错误次数，显著缩短水迷宫实验中小鼠找到安全台的时间，显著增加正确反应次数，对小鼠自发活动没有显著的影响。双侧颈总动脉完全结扎致大鼠记忆障碍实验中，PIF显著减少八臂放射状迷宫中工作记忆错误次数（WME）、参照记忆错误次数（RME）和总错误次数（TE），缩短大鼠摄食时间（Time）；在Morris水迷宫定向游泳实验中缩短大鼠找到安全台的潜伏期，增加probe test中大鼠在原安全台所在象限中的停留时间，缩短工作记忆测试中大鼠找到安全台的潜伏期；显著延长避暗实验中大鼠进入暗室的潜伏期。表明PIF明显改善脑血流长期低灌注引起的记忆障碍。病理组织学检查表明，模型组大鼠大脑皮质和海马CA3区可见多数神经元空泡样变，核膜增厚，血管内皮细胞轻度肿胀；而PIF各剂量组大鼠大脑皮质和海马CA3区空泡样变的神经元数均较模型组明显减少，染色质分布均匀，轴突较为明显，毛细血管基本正常。提示PIF对脑细胞缺血性损伤有保护作用。PIF能够显著降低反复缺血再灌小鼠脑组织中NOS活性和NO含量；增强双侧颈总动脉结扎大鼠脑组织中乳酸脱氢酶（LDH）活性，降低乳酸（LA）含量；增强Ca²⁺-ATPase活性；改善急性血瘀模型大鼠血液流变学各项指标。 综上所述，PIF有抗脑血管性痴呆的作用，其机制可能与改善中枢胆碱能神经系统功能、降低NOS活性、降低NO含量、增强LDH活性、降低LA含沈阳药科大学硕士学位论文 摘要量、增强C八ATPase活性及改善血液流变学等作用有关。 DZ显著减少反复脑缺血再灌小鼠跳台实验V；【练和测试阶段的错误次数，显著延长测试阶段的潜伏期，显著减少避暗实验中测试阶段的错误次数，缩短水迷宫中找到安全台的时间和增加正确反应次数；改善东南著碱旧CPL)导致的记忆获得障碍和空间记忆障碍、亚硝酸钠（NaNOZ）导致的记忆巩固障碍、30％乙醇导致的记忆再现障碍。DZ对脑缺血致记忆障碍的改善作用可能与降低脑组织中NOS活性和NO含量有关。DZ在抗VD的多项测试中均具有与PIF相同的药理作用，提示DZ是PIF抗血管性痴呆的活性成分之一。更多还原

【Abstract】 The effects of anti-vascular dementia of Puerariae Isoflavone (PIF) and the mechanism of this medicine were preliminarily studied. The effects of Daidzein (DZ), one of components of PIF, on the memory of mice were also studied in this paper. The results indicated PIF reduced numbers of errors in mice performed cerebral ischemia-reperfusion in step-down test and step-through test. PIF decreased the time of swimming from the original area to the goal area and increased the numbers of right reflects in water maze in mice performed incomplete occlusion of bilateral carotid common artery in company with vagus nerves. Additionally, PIF was as effective in this model of mice as that of in mice performed ischemia-reperfusion in step-down test and step-through test. The numbers of working memory errors (WME), reference memory errors (RME) and total errors (TE) were increased obviously and time of fetching- food (Time) was prolonged markedly in rats performed bilateral carotid common artery occlusion (BCCAO) in eight-arm radial maze. These changes were prevented by administration of PIF. In Morris water maze PIF shortened the latency of searching the hidden platform in directional swirnming test, increased the time spent swimming in the target quadrant during 90s in probe test, and reduced the latency of arriving to the goal platform in working memory test. Moreover, PIF prolonged the latency of entry into dark room in step-through test in rats performed BCCAO. PIF prevented the nerve cell from the ischemic damages on the basis of pathology. The increase of nitric oxide (NO) and enhance of NOsynthase (NOS) activity in mice performed cerebral ischemia-reperfusion were significantly prevented by administration of PIF. PIF inhibited the depression of the lactic dehydrogenase (LDH) activity, the enhancement of lactic acid (LA) and depression of calcium pump (Ca2+-ATPase ) activity in the cerebrum of the rats performed BBCAO. PIF ameliorated indexes of blood rheology including high, mid and low whole blood viscosity, whole blood reduction viscosity and erythrocyte electrophoresis time(EET).Summarizing all the experimental results, PIF showed anti-vascular dementia effects. The mechanism maybe involved inhibiting toxicity of NO, releasing the obstruction of energy metabolism, improving the blood rheology.DZ reduced numbers of errors and prolonged the latency of mice performed cerebral ischemia-reperfusion in step-down test and step-through test. The time of swimming from the original area to the goal area was decreased and the numbers of right reflect were increased by DZ administration in water maze. Additionally, DZ significantly antagonized the amnesia induced by scopolamine (SCPL), NaNO2 and ethanol in mice. The increase of nitric oxide (NO) and enhance of NO synthase (NOS) activity in mice performed cerebral ischemia-reperfusion were significantly prevented by administration of DZ. These results indicated that DZ had the effect of improving memory in mice as one effective component of PIF.更多还原