目的观察毛冬青提取物(pubescent holly root extract,PHRE)对血管性痴呆(VD)模型小鼠学习记忆能力的影响,探讨其潜在的作用机制。方法采用反复夹闭、再通双侧颈总动脉同时尾静脉放血的方法制备小鼠痴呆模型,随后将小鼠随机分为假手术组,模型组,尼莫地平对照组(30 mg·kg~(-1)),毛冬青低、中、高剂量组(5,10,20 g·kg~(-1)),各组灌胃相应药物10 m L·kg~(-1),连续35 d,从第30天开始进行行为学检测,末次给药后收集大脑样本,HE染色观察病理学变化、免疫组化法及Western Blot法检测Bcl-2、Bax蛋白表达。结果与假手术组比较,模型组小鼠的恐惧记忆时间明显缩短,大脑海马区神经元细胞病变严重,海马区Bcl-2/Bax蛋白表达的比值降低,且主要分布于胞质。与模型组比较,各药物组小鼠的恐惧记忆时间明显延长,大脑海马区的组织病变情况改善,且海马区Bcl-2/Bax蛋白表达的比值显著增加。结论毛冬青提取物可能通过上调Bcl-2蛋白表达,下调Bax蛋白表达,减少细胞凋亡,保护神经细胞,从而改善血管性痴呆小鼠的学习记忆功能。 Objective To investigate the effect of pubescent holly root extract (PHRE) on the learning and memory abilities of vascular dementia (VD) model mice and to explore its potential mechanism. Methods The model of dementia in mice was prepared by repeated clipping and then through the common carotid arteries of both sides of the carotid artery. The mice were then randomly divided into sham operation group, model group, nimodipine control group (30 mg · kg ~ (-1), Mao Dongqing low, medium and high dose groups (5, 10, 20 g · kg -1) d. Behavioral tests began on the 30th day. Brain samples were collected after the last administration. The pathological changes were observed by HE staining. The expressions of Bcl-2 and Bax protein were detected by immunohistochemistry and Western Blot. Results Compared with the sham operation group, the fear memory time in the model group was significantly shortened. The neuronal cells in the hippocampus were severely damaged. The ratio of Bcl-2 / Bax protein expression in the hippocampus was decreased and mainly distributed in the cytoplasm. Compared with the model group, the fear memory time of each drug group was significantly prolonged, the histopathological changes in the hippocampus of the brain were improved, and the ratio of Bcl-2 / Bax protein expression in the hippocampus was significantly increased. Conclusion Mao dongqing extract may improve the learning and memory function of vascular dementia mice by up-regulating Bcl-2 protein expression, down-regulating Bax protein expression, decreasing apoptosis and protecting nerve cells.