复智胶囊对血管性痴呆模型大鼠学习记忆能力改善的作用机制

目的： 观察复智胶囊对血管性痴呆大鼠学习记忆能力，胆碱乙酰转移酶（CHAT）活性、突触素（synaptophysin，P₃₈）表达及海马突触显微结构的影响，探讨复制胶囊改善学习记忆能力的作用机制。 方法： SPF级雄性SD大鼠采用双侧颈总动脉永久结扎法（2-VO）制备血管性痴呆大鼠模型。选取造模成功的大鼠，随机分为模型组、多奈哌齐组、复智胶囊高剂量组、复智胶囊低剂量组，并设假手术对照组。连续灌胃4周后采用Morris水迷宫进行行为学检测，同时采用免疫组化方法检测海马CHAT和P₃₈的表达，采用Golgi染色法检测大鼠海马神经元突触显微结构形态及树突棘数量的变化。 结果： 与假手术组相比，造模后各组大鼠学习记忆能力均有下降，逃避潜伏期和游泳路程明显延长，撤除平台后跨越原平台次数明显减少，海马 CHAT活性和P₃₈表达明显下降，海马神经元细胞树突棘数量减少（P<0.05）；而与模型组相比，复智胶囊高、低剂量组和多奈哌齐组大鼠学习记忆能力均有改善，逃避潜伏期和游泳路程均有缩短，跨越原平台次数明显增多，CHAT活性和P₃₈表达明显增高，树突棘数量均有增多（P<0.05）。 结论： 复智胶囊对血管性痴呆大鼠学习记忆能力有一定的改善作用，可能是通过提高胆碱能系统活性，增加突触素蛋白表达，促进海马突触显微结构重建来实现的。

Mechanism of Fuzhi Capsule on Improving Learning and Memory Ability of Rats with Vascular Dementia

Objective: To observe the effect of Fuzhi capsule on learning and memory ability of rats with vascular dementia, the activity of choline acetyltransferase (CHAT), the expression of synaptophysin (P₃₈) and hippocampal synaptic microstructure, and to explore the mechanism of Fuzhi capsule on improving the ability of learning and memory. Method: The SPF male SD rats were divided into model group, Donepezil group, Fuzhi capsule high and low dosage groups, and sham operation control group randomly.The vascular dementia model was established by permanent bilateral common carotid artery ligation (2-VO). Drugs were administered to rats by gastric perfusion once a day for 4 weeks. Then all the rats were detected the behavior by Morris water maze, the expression of CHAT and P₃₈ in hippocampus by immunohistochemistry, the synapse microstructure of hippocampal neurons and the number of dendritic spines by Golgi staining. Result: Compared with the sham operation group, the learning and memory ability of rats in model group were decreased, the escape latency and swimming distance were significantly prolonged, the number of across the platform after remove platform was decreased, the activity of CHAT and the expression of P₃₈ in hippocampus were decreased, the number of dendritic spines in the hippocampus neurons was reduced (P<0.05). Compared with the model group, the learning and memory ability of rats in Fuzhi capsule high and low dosage group and donepezil group were improved, the escape latency and swimming distance were shortened, the number of across the platform after remove platform was increased obviously, the activity of CHAT and the expression of P₃₈ in hippocampus was increased, the number of dendritic spines was increased (P<0.05). Conclusion: Fuzhi capsule can improve the learning and memory ability of rats with vascular dementia by increasing the activity of CHAT and the expression of P₃₈ in hippocampus, and promote hippocampal synaptic microstructure reconstruction.