肝X受体对慢性脑缺血致学习记忆障碍保护作用的研究进展

Effects of Liver X Receptor on Learning and Memory Impairment Induced by Chronic Cerebral Ischemia

慢性脑缺血(CCH)是指各种原因引发的长期脑血流灌注不足,在血管性痴呆(VD)、阿尔茨海默病(AD)等多种神经系统疾病的发生发展过程中起着重要的作用。CCH为临床常见病、多发病,其致死率、致残率高,可导致认知功能障碍,严重危害人类健康。针对CCH的治疗已迫在眉睫,然而迄今为止,CCH导致认知功能障碍的发病机理不完全清楚,尚无特效药物和治疗手段,因此,CCH导致认知功能障碍的发病机制与防治是神经科学关注的焦点。肝X受体(LXRs)是孤核受体超家族成员,包括LXRα和LXRβ两种亚型,可被氧化固醇类激活而发挥调节人体胆固醇的作用。此外,它还参与调节人体众多的生理活动,包括脂肪形成,糖代谢和炎症反应等。随着研究的深入又发现LXRs在CCH所致学习记忆障碍中发挥重要的保护作用。本文从LXRs的结构、功能及其在CCH所致学习记忆障碍中发挥保护的机制进行综述,为CCH所致学习记忆障碍提供新的治疗靶点和理论依据。

Chronic cerebral hypoperfusion( CCH) refers to the long-term cerebral blood perfusion insufficiency caused by various reasons,which plays an important role in the occurrence and development of vascular dementia,alzheimer’s disease and other neurological diseases. It is a common and frequently-occurring disease with high mortality and disability,which can lead to cognitive impairment and seriously endanger human health. Treatment for CCH is imminent,yet so far,the pathogenesis of cognitive impairment caused by CCH is not completely clear,and there is no specific drug or treatment. The pathogenesis and prevention of cognitive impairment caused by CCH are the focus of neuroscience. Liver X receptors( LXRs) are the members of the superfamily of solitoid-nucleus receptors,including two subtypes of LXR alpha and LXR beta. They are activated by oxidized sterols and play a role in regulating human cholesterol. In addition,it is also involved in the regulation of a variety of physiological activities,including fat formation,sugar metabolism and inflammatory response. With the deepening studies,it has been found that LXRs play an important protective role in CCH induced learning and memory disorders. In this paper,the structure and function of LXRs and its mechanism of protection in CCH induced learning and memory disorders were reviewed in order to provide a new therapeutic target and theoretical basis for learning and memory impairment caused by CCH.