肌肽对皮层下缺血性血管性痴呆动物认知功能的保护作用

摘要

Aim Subcortical ischemic vascular demen-tia ( SIVD ) induced by chronic hypoperfusion due to small-artery disease is a common cause of vascular de-mentia ( VaD) , which is recognized as the second most prevalent type of dementia. The aim of this study was to determine whether carnosine played a protective role in cognitive impairment induced by permanent occlu-sion of the right unilateral common carotid arteries ( rUCCAO ) in SIVD. Methods Adult male mice ( C57BL/6 strain ) were subjected to rUCCAO, and treated with carnosine or saline. Locomotor test, open field test, hot plate test, freezing test and Morris water maze were performed after rUCCAO. Results There were no differences among rUCCAO group, carnosine group and sham group for total distance traveled in lo-comotor test. In the open field test, carnosine (200, 500 mg · kg-1 ) significantly revised the decrease of latency spent in the center induced by SIVD . There were no differences between rUCCAO and sham groups for the pain threshold. In freezing test, rUCCAO in-duced a significant reduction in content memory, which was completely reversed by treatment of carnosine. In Morris water maze training trials, rUCCAO-treated mice showed prolonged escape latency in acquisition phase, carnosine ( 200, 500 mg · kg-1 ) markedly shortened the escape latency. Conclusion These data suggest that carnosine has a neuroprotective effect on cognitive impairment induced by rUCCAO in mice.%目的：探讨肌肽对皮层下缺血性血管性痴呆动物的认知功能的作用。方法永久性结扎小鼠单侧颈总动脉建立皮层下缺血性血管性痴呆模型后饲养28 d,期间隔天给予肌肽(200、500、750 mg·kg-1)或生理盐水,采用运动量监测、敞箱实验、热板实验,恐惧记忆、水迷宫模型检测小鼠行为学指标。结果与假手术组相比,手术组动物的运动量和疼痛阈值没有改变；其中肌肽(200、500 mg·kg-1)能明显延长小鼠在敞箱实验中的探索时间,逆转手术引起的动物恐惧记忆中背景记忆能力的下降,并明显改善手术引起的水迷宫实验中动物的学习记忆能力的下降。结论单侧颈总动脉结扎所致的皮层下缺血性血管性痴呆会导致认知功能障碍,肌肽对皮层下缺血性血管性痴呆动物的认知功能有明显的保护作用。