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目的:观察甲基莲心碱(neferine,Nef)对慢性脑缺血大鼠的学习记忆功能的影响及海马功能区Notch1和SYN蛋白表达的影响。方法:雄性SD大鼠(250-300g)随机分为假手术(Sham)组,模型(Mod)组,尼莫地平(nimodipine,Nim)阳性对照组,Nef治疗组,每组5只。采用双侧颈总动脉永久性结扎(Bilateral common carotid artery ligation,2-VO)建立慢性脑缺血模型,术后第1天口服给予NS(5 mg·kg~(-1)),Nim(1 mg·kg~(-1)),Nef(20 mg·kg~(-1))至21 d。记录大鼠体质量变化;Nissel染色观察大鼠海马神经元数量变化;Morris水迷宫法检测大鼠学习记忆功能;IHC和Western blot分析海马Notch1和SYN蛋白的表达水平的变化。结果:与Mod组比较,Nef可以明显改善2-VO诱导大鼠在21 d的体质量减轻,海马CA1区神经元数量减少,寻找平台路线和时间、逃避潜伏期延长,跨越平台次数降低,且优于Nim(P<0.05);Nef可明显上调2-VO诱导的大鼠在第21天时海马CA1区Notch1和SYN蛋白表达降低。结论:Nef可有效改善2-VO诱导的CCl大鼠学习记忆功能障碍,其机制可能与增强海马CA1区Notch1信号通路,增强突触可塑性有关。
Objective: To observe the effects of neferine (Nef) on learning and memory in chronic cerebral ischemia rats and the expression of Notch1 and SYN in hippocampus. Methods: Male SD rats (250-300g) were randomly divided into Sham group, Mod group, nimodipine (Nim) positive control group and Nef treatment group, with 5 rats in each group. The model of chronic cerebral ischemia was established by bilateral common carotid artery ligation (2-VO). NS (5 mg · kg -1), Nim (1 mg · kg -1) and Nef (20 mg · kg -1) for 21 days. The change of body weight of rats was recorded. The number of hippocampal neurons was observed by Nissel staining. The learning and memory function of rats was detected by Morris water maze. The expression of Notch1 and SYN protein in hippocampus was detected by IHC and Western blot. Results: Compared with Mod group, Nef significantly reduced the body weight, the number of neurons in hippocampal CA1 area, the platform route and time, the escape latency and the number of crosses across the platform, (P <0.05); Nef significantly up-regulated the expression of Notch1 and SYN in hippocampal CA1 region in 2-VO-induced rats on day 21. CONCLUSION: Nef can effectively improve 2-VO-induced learning and memory dysfunction in CCl rats, which may be related to the enhancement of Notch1 signaling pathway in hippocampal CA1 region and enhancement of synaptic plasticity.