胆碱酯酶抑制剂对血管性痴呆大鼠认知功能的影响

目的观察胆碱酯酶抑制剂对血管性痴呆(VaD)大鼠海马CA1区细胞凋亡、血管内皮生长因子(VEGF)及神经元型一氧化氮合酶(nNOS)的影响。方法将45只雄性SD大鼠,随机分为假手术组、模型组、治疗组,每组15只大鼠。采用双侧颈总动脉永久性结扎法建立VaD模型,假手术组和模型组用生理盐水2 ml灌胃,治疗组用多奈哌齐进行灌胃。造模后1个月,采用Morris水迷宫检测大鼠的学习记忆能力,用TUNEL检测海马CA1区神经细胞凋亡,用免疫组织化学染色方法检测大鼠海马CA1区VEGF、nNOS阳性细胞表达。结果与模型组比较,假手术组和治疗组大鼠第2天起逃避潜伏期明显缩短;海马CA1区神经细胞凋亡显著减少;海马CA1区VEGF和nNOS阳性细胞表达明显升高,差异有统计学意义(P<0.05)。结论多奈哌齐可能通过减少VaD大鼠海马CA1区细胞凋亡,上调VEGF、nNOS的表达,从而改善VaD大鼠的认知功能。

Effect of acetylcholinesterase inhibitor on cognitive function in rats with vascular dementia

Objective To observe the effect of acetylcholinesterase inhibitor,donepezil,on apoptosis of neurons in hippocampal CA1,vascular endothelial growth factor(VEGF) and neuronal nirtic oxide synthase(nNOS) in rats with vascular dementia(VaD).Methods Forty-five male SD rats were randomly divided into sham operation group,model group,treatment group(15 in each group).A VaD model was established by ligating bilateral common carotid arteries.Learning and memory ability of rats in treatment group were observed by Morris water maze test 1 month after intragastric donepezil.Apoptosis of neurons in hippocampal CA1 was detected with TUNEL staining. Expression levels of VEGF and nNOS in hippocampal CA1 were measured by immunohistochemistry. Results The escape latent period was significantly shorter,the number of apoptotic neurons in hippocampal CA1 was significantly less,and the expression levels of VEGF and nNOS in hippocampal CA1 were significantly higher in sham operation group and treatment group than in model group(P < 0.05 ).Conclusion Donepezil up-regulates the expression of VEGF and nNOS by reducing the apoptosis of neurons in hippocampal CA1 of rats with VaD,thus improving their cognitive function.