丹皮酚对皮质下缺血性血管性痴呆小鼠认知功能的保护作用及机制

Protective effect and mechanism of paeonol on cognitive function in the mice with subcortical ischemic vascular dementia

目的探讨丹皮酚对皮质下缺血性血管性痴呆(subcortical ischemic vascular dementia,SIVD)小鼠的认知功能的作用及机制。方法小鼠随机分为假手术组、模型组、丹皮酚低剂量与高剂量组,以永久性结扎小鼠单侧颈总动脉建立皮质下缺血性血管性痴呆模型,假手术组只分离右颈总动脉,不进行血管结扎。期间每天给予生理盐水或丹皮酚(20、40 mg/kg),以开放场实验、水迷宫等方法检测小鼠行为学变化,以分光光度计法检测海马组织匀浆胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AChE)活性。结果与假手术组比较,手术组小鼠的运动量没有改变(P>0.05)。与模型组比较,其中丹皮酚高剂量(40 mg/kg)能明显延长SIVD小鼠在中心区活动中的探索时间,并改善SIVD小鼠学习记忆能力下降,表现为丹皮酚(40 mg/kg)治疗后小鼠Morris水迷宫逃避潜伏期缩短,穿越原平台时间以及穿台次数均增多(P<0.05)。此外,与模型组比较,丹皮酚(40 mg/kg)治疗还能降低SIVD小鼠海马组织AChE活性,升高ChAT活性(P<0.05)。而与模型组比较,丹皮酚(20 mg/kg)治疗则各指标没有显著性差异(P>0.05)。结论丹皮酚对SIVD小鼠认知功能下降具有保护作用,其机制可能与增加胆碱递质合成,减少胆碱递质分解有关。

Objective To investigate the effect and mechanism of paeonol on cognitive function in the mice with sub- cortical ischemic vascular dementia（SIVD）. Methods The mice were randomly divided into sham operation group, model group, paeonol low dose group and paeonol high dose group. The model of subcortical isehemic vascular dementia was established by permanent ligation of unilateral common carotid arteries in mice. In the sham operation group, only the right common carotid artery was isolated and no vascular ligation was performed. During the period, the mice were daily given normal saline or paeonol （20, 40 mg/kg）. The behavioral changes of mice were detected by open field test and water maze. The activities of homogenate choline acetyltransferase（ChAT） and acetylcholinesterase（AChE） in hippocampus tissue were detected by spectrophotometer. Results Compared with the sham operation group, there was no change in the exercise amount of the mice in the operation group （P〉0.05）. Compared with the model group, paeonol （40 mg/kg） could significantly prolong the exploration time of SIVD mice in the central area, and improve the decreasing learning and memory ability of SIVD mice. It shown that the escape latency of Morris water maze was reduced in the mice after paeonol treatment （40 mg/kg）, and the crossing platform time and the number of crossing were increased （P〈0.05）. In addition, compared with the model group, paeonol（40 mg/kg） could decrease AChE activity and increase ChAT activity in hippocampus of SIVD mice（P〈0.05）. Compared with the model group, there was no significant difference in all indicators in paeonol （20 mg/kg） treatment（P〉0.05）. Conclusion Paeonol has a protective effect on the decline of cognitive function in SIVD mice. The mechanism may be related to the increase of synthesis of cholinergic neurotransmitters and the decrease of decomposition of cholinergic transmitter.