蛇床子素对痴呆模型小鼠行为学的保护作用

Effects of Osthole on Ethology in Mouse Model of Dementia

目的:研究蛇床子素(Osthole,Ost)对老年性痴呆、血管性痴呆模型小鼠行为学的保护作用及其作用机制。方法:采用一次性侧脑室注射β-淀粉样蛋白(β-amyloid protein,Aβ25-35)及脑缺血再灌注(短暂性夹闭小鼠双侧颈总动脉)两种方法,分别制备拟老年性痴呆和拟血管性痴呆小鼠模型。治疗组每天腹腔注射(ip)蛇床子素(15,7.5 mg·kg-1),连续10 d。通过Morris水迷宫、探索运动等行为学实验,观察小鼠空间学习记忆和空间探索能力的变化,并测定小鼠脑组织一氧化氮(nitric oxide,NO)含量和一氧化氮合酶(nitric oxide synthase,NOS)活性。结果:蛇床子素(15,7.5 mg·kg-1,ip)可明显改善两种痴呆模型小鼠的行为障碍(P<0.01,P<0.05),并可不同程度的降低小鼠脑组织的NO含量和NOS活性(P<0.01)。结论:蛇床子素(15,7.5 mg·kg-1,ip)可改善侧脑室注射Aβ25-35致老年性痴呆、脑缺血再灌注致血管性痴呆模型小鼠的空间学习记忆和探索能力障碍,其作用机制可能与降低脑组织NO水平有关。

Objective:To examine the protective effect and the potential mechanism of osthole(Ost)on the behavioral disorders in presenile and vascular dementia model mice.Methods:Icy injection of β-amyloid peptide(Aβ25-35)once to mice was used as a presenile dementia animal model. Temporary bilateral common carotid arteries obstruction was used as a repeated cerebral ischemia-reperfusion model. Mice were treated with osthole(15,7.5 mg·kg-1)for 10 days and the spatial learning and memory as long as the spatial exploration abilities were assessed via. Morris water maze test and exploratory movement test respectively. The levels of nitric oxide(NO)and nitric oxide synthase(NOS)were also measured. Results:Osthole significantly improved the behavioral disorders in both dementia models(P<0.01 or P<0.05). Osthole(15,7.5mg·kg-1)also decreased the level of NO and NOS in the mice brain(P<0.01). Conclusion:Osthole can improve the spatial learning and memory and spatial exploration abilities in two mice models of dementia,which is related to decrease NO and NOS levels.