【作者】 张玉丽；

【导师】 邹莉波；

【作者基本信息】 沈阳药科大学 ， 药理学， 2007， 硕士

【摘要】 目的：本文主要对LST的抗血管性痴呆作用进行了药效学研究，并初步探讨了其作用机制。方法：采用行为药理学实验方法——跳台法、避暗法、Y迷宫法和水迷宫法等考察LST对小鼠缺血-再灌注致痴呆模型、对大鼠大脑中动脉电凝致痴呆模型以及大鼠多发梗塞型痴呆模型的改善作用；采用大鼠颈动-静脉旁路血栓形成实验、小鼠体内血栓形成实验来考察LST对血栓形成的影响。结果：实验结果表明，在缺血-再灌注致小鼠痴呆实验中，LST显著减少避暗实验和跳台实验中小鼠的错误次数、总电击时间，并显著延长潜伏期，显著缩短水迷宫实验中找到安全台的时间，增加正确反应次数；在大脑中动脉电凝和多发梗塞致大鼠痴呆实验中，LST能显著提高大鼠Y迷宫实验中自发交替反应的正确反应率，显著缩短Morris水迷宫实验的定向游泳实验中大鼠找到安全台的潜伏期，增加probe test中在原安全台所在象限的停留时间，显著延长避暗实验中大鼠进入暗室的潜伏期，提示LST可显著改善血管性痴呆模型动物学习记忆功能。在大鼠大脑中动脉电凝致痴呆实验中，模型组大鼠大脑皮质及海马CA1区神经元稀疏，水肿，轴突消失，尼氏小体不明显，而LST能显著改善上述病理改变，提示LST能保护大脑皮质及海马神经细胞免受缺血缺氧的损害。LST能够显著降低缺血-再灌注小鼠脑组织中MDA含量，增加SOD活性。此外，LST还具有一定的抗血栓作用。结论：LST具有抗血管性痴呆作用，其机制可能与缓解脑缺血、缺氧状态，减少活性氧的生成，提高脑组织抗氧化酶活力，抑制脂质过氧化反应相关。更多还原

【Abstract】 Objective: The purpose of this paper was to study the anti-vascular dementia effects of LST and its mechanism. Methods: Using the methods of behavioral pharmacology including the one-trial step-down and the step-through passive advoidance test, Y-maze test and the water maze test to investigate the effects of LST against the vascular dementia induced by cerebral ischemia reperfusion in mice, middle cerebral artery occlusion(MCAO) model in rats and multi-infarct dementia (MID) model in rats. Furthermore, the antithrombtic effect of LST was also detected. Results: It reduced numbers of errors in step-down test, prolonged the latency of entry into dark room in step-through test, decreased the time of swimming from the original area to the goal area and increased the numbers of right reflects in water maze task in mice performed cerebral ischemia-reperfusion. In Morris water maze task LST shortened the latency of searching the hidden platform in directional swimming test and increased the time spent swimming in the target quadrant during 90s in probe test in rats performed MCAO and MID. Moreover, LST prolonged the latency of entry into dark room in step-through test and increased the percent alternation in Y maze task in these rats. Furthermore, a correlation between histological injury and behavioral deficits was shown pathologically. The increase of contents of malonic aldehyde (MDA) and the inhibition of superoxide dismutase (SOD)’s activity in the cerebrum in mice performed cerebral ischemia-reperfusion were significantly prevented by the administration of LST .Conclusion: Summarizing all the experimental results, LST showed the anti-vascular dementia effects. The mechanism maybe involve relieving the condition of cerebral ischemia, inhibiting the oxygen free radical reaction,elevating the activity of antioxidase in brain.更多还原