齐墩果酸唤醒阿尔兹海默病大鼠海马沉默突触作用及机制研究

Research on effects and mechanisms of oleanolic acid on waking silent synapses in Alzheimer's disease rat hippocampus

目的:探讨齐墩果酸唤醒阿尔兹海默病(AD)大鼠沉默突触而改善其认知功能的作用及初步机制。方法:选用雄性SD大鼠,经侧脑室注射Aβ25-35建立AD模型,通过水迷宫实验检测大鼠空间学习与记忆能力,采用透视电镜观察神经元及突触超微结构,Western blot检测钙调蛋白激酶Ⅱ(Ca MKⅡ)、蛋白激酶C(PKC)、脑源性神经营养因子(BDNF)以及酪氨酸激酶受体B(Trk B)蛋白表达。结果:与正常组比较,模型组大鼠的逃避潜伏时间明显延长(P<0.01),空间学习与记忆能力明显下降,神经元与突触超微结构损伤明显,Ca MKⅡ、PKC、BDNF及Trk B蛋白表达明显减少(P<0.01);与模型组比较,齐墩果酸组大鼠的逃避潜伏时间明显缩短(P<0.01),学习与记忆能力显著提高,神经元与突触超微结构损伤减轻,Ca MKⅡ、PKC、BDNF及Trk B蛋白表达明显增加(P<0.01)。结论:齐墩果酸可有效改善AD大鼠的空间学习与记忆能力,该作用可能与减轻神经元及突触超微结构损伤和唤醒沉默突触有关。

Objective：To investigate effects and preliminary mechanisms of oleanolic acid on waking silent synapses in Alzheimer＇s disease（AD） rat to improve its cognitive function.Methods：Sprague-Dawley（SD） male rats were administrated with intracerebroventricular injection of Aβ25-35 to establish AD model.Morris water maze was used to test rat＇s spatial learning and memory.Neurons and synaptic ultrastructure were observed by electron microscopy.Then the expression of calmodulin protein kinase I（Ca MK I）,protein kinase C（PKC）,brain-derived neurotrophic factor（BDNF） and tyrosine kinase receptor B（Trk B） protein were detected by Western blot.Results：Compared with the control group,the escape latency of model group was significantly prolonged（P〈0.01）,indicating that spatial learning and memory was decreased.Moreover,in the model group,the neuronal and synaptic ultrastructure were obviously damaged and the expression of Ca MKⅡ,PKC,BDNF and Trk B protein were significantly reduced（P〈0.01）.Compared with the model group,the escape latency of oleanolic acid group was significantly shortened（P〈0.01）,indicating that spatial learning and memory was improved,the neuronal and synaptic ultrastructure damage was extenuated,and the expression of Ca MK I,PKC,BDNF and Trk B protein were significantly increased（P〈0.01）.Conclusion：Oleanolic acid can improve spatial learning and memory of AD rats,which may be related to mitigate neurons and synaptic ultrastructure damage and wake silent synapses.