TRP 对KA 诱导的AD 模型大鼠学习记忆的影响及其作用机制

目的:观察雷公藤甲素(Triptolide,TRP)对海人藻酸(Kainic acid,KA)海马内注射后大鼠学习记忆的影响及其作用机制。方法:采用Morris水迷宫筛选空间学习记忆能力正常的SD雄性大鼠90只(200～220g)。将实验动物分成3组:右侧海马注射生理盐水后生理盐水灌胃对照组(NS+NS)、右侧海马注射海人藻酸后生理盐水灌胃干预组(KA+NS)、右侧海马注射海人藻酸后雷公藤甲素灌胃干预组(KA+TRP)。动物存活1天,3天,5天,7天,14天,每个时间点6只,处死前分别于各相应时间点用Morris水迷宫检测各组动物空间位置记忆能力;免疫组织化学方法结合图像分析技术检测海马CA1区神经元COX-2的表达。结果:与NS组(NS+NS)比较,KA组(KA+NS)大鼠逃避潜伏期延长(P<0.05),跨越原平台次数减少(P<0.05);海马CA1区的神经元COX-2表达升高(P<0.05);TRP组(TRP+KA)与KA组比较,大鼠的平均逃避潜伏期从第5天起缩短(P<0.05),跨越原平台次数增多(P<0.05),海马CA1区神经元COX-2表达在5天,7天时下调(P<0.05)。结论:KA海马内注射,可以导致大鼠学习记忆功能障碍及上调海马CA1区神经元COX-2表达;雷公藤甲素干预治疗,能够改善动物的学习和记忆能力,能抑制KA诱导的海马CAl区神经元COX-2的表达。

Effects of Triptolide on Learning and Memory and its Mechanism on AD Rats Induced by KA

Objective: To observe the effects of triptolide(TRP) on learning and memory of rats induced by injection of kainic into hippocampus and its mechanism.Methods: 90 SD rats with normal learning and memory were selected by Morris water maze method,and then divided randomly into three groups: NS treated after NS injection into the right dorsal hippocampus group(NS+NS,n=30);NS treated after KA injection into the right dorsal hippocampus group(KA+NS,n=30);TRP treated after KA injection into the right dorsal hippocampus group(KA+TRP,n=30).The animals were sacrificed at d1,d3,d5,d7,d14 after KA injection,6 rats for each time point.The behavior of rats was detected by Morris water maze before sacrificed.COX-2 expression in CA1 region of hippocampus was investi-gated by immunohistochemistry and computer image analysis methods.Results: Compared with that of NS+NS group,a significant in-crease in the mean escape latencies of rats and an obvious decrease in frequency of passing through the platform of rats occurred in KA+NS group(P<0.01).COX-2 expression of CA1 hippocampus obviously increased in KA+NS group(P<0.01).Compared with KA+NS group,the mean escape latencies of rats decreased and the frequency of passing through the platform of rats increased at d 5,d 7,d 14 in KA+TRP group(P<0.05).COX-2 expression in CA1 hippocampus significantly decreased at d 5,d 7 in KA+TRP group(P<0.05).Conclusion: Kainic acid can contribute to the decreased learning and memory and the increased expression of COX-2 in area CA1 of the hippocampus in vivo.Treatment with tritolide can inhibit the expression of COX-2 which was induced by kainic acid in CA1 area of hip-pocampus.