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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。
Objective: To observe the effects of Fuzhi Capsule on learning and memory ability, CHAT activity, synaptophysin (P38) expression and hippocampal synapse microstructure in vascular dementia rats. To explore the effects of Fuzhi Capsule on learning and memory, The mechanism of memory ability. Methods: Male Sprague-Dawley (SD) rats were used to establish a rat model of vascular dementia by permanent bilateral carotid artery ligation (2-VO). Rats were selected and randomly divided into model group, donepezil group, Fuzhi Capsule high dose group and Fuzhi Capsule low dose group, and a sham operation control group was established. Morris water maze was used to conduct behavioral testing four weeks after continuous gavage. At the same time, immunohistochemistry was used to detect the expression of CHAT and P38 in hippocampus. Golgi staining was used to detect the synapse microstructure and the number of dendritic spines The change. Results: Compared with the sham-operated group, the learning and memory abilities of rats in each group were decreased, the escape latency and swimming distance were significantly prolonged, the number of traversing the platform was significantly decreased, the CHAT activity and P38 expression in hippocampus were significantly decreased, The number of dendritic spines in hippocampal neurons was decreased (P <0.05). Compared with the model group, the learning and memory abilities of high, low dose and donepezil groups were improved, the escape latency and swimming distance were shortened , The number of crossing the original platform increased significantly, CHAT activity and P38 expression was significantly increased, the number of dendritic spines have increased (P <0.05). Conclusion: Fuzhi Capsule can improve the learning and memory abilities of rats with vascular dementia by improving the activity of cholinergic system, increasing the expression of synaptophysin and promoting the synaptic microstructure reconstruction in hippocampus.