Sigma 1受体对血管性痴呆小鼠血脑屏障的调节作用及机制研究

项目名称： Sigma 1受体对血管性痴呆小鼠血脑屏障的调节作用及机制研究

项目编号： No.81503057

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 迟天燕

作者单位： 沈阳药科大学

项目金额： 17.9万元

中文摘要： 血管性痴呆(Vascular Dementia, VD)是继阿尔茨海默病后引起痴呆的第二大原因。血脑屏障结构和功能的变化是VD病理变化的重要环节之一。星形胶质细胞作为神经血管单元中重要的组成部分是维持血脑屏障稳定性的必要条件。Sigma 1受体（σ1R）广泛分布于中枢神经系统, 在神经元和胶质细胞中丰富表达。有报道，缺血性脑卒中后σ1R在星形胶质细胞中高表达。本课题组前期研究表明，σ1R激动剂PRE084能通过上调全脑缺血再灌注模型小鼠海马突触相关蛋白及脑源性神经营养因子的表达并减少神经元的缺失，显著改善VD模型小鼠的学习记忆障碍，但它是否与保护星形胶质细胞进而维持血脑屏障的功能和完整性有关尚不清楚。本课题将利用σ1R特异性激动剂和拮抗剂以及σ1R基因敲除小鼠，深入研究σ1R在全脑缺血再灌注致VD模型中，对血脑屏障保护作用的影响和星形胶质细胞的调节作用机制。

中文关键词： sigma-1受体；血管性痴呆；血脑屏障；星形胶质细胞；学习记忆

英文摘要： Vascular dementia (Vascular Dementia, VD) is the second largest cause of dementia after Alzheimer's disease. Changes in the structure and function of the blood-brain barrier is an important part of VD pathology. As an important component of the neurovascular unit, astrocytes is necessary for maintaining the stability of the blood-brain barrier. The sigma 1 receptors (σ1R) is strongly expressed in neurons and glial cells within the central nervous system. It has been reported that σ1R are highly expressed in astrocytes after ischemic stroke. In previous study, we had confirmed that σ1R agonist PRE084 can significantly increase the expression of synapse-associated proteins and brain derived neurotrophic factor, reduce neuronal cell damage, and significantly improve learning and memory impairments in VD mice induced by global cerebral ischemia and reperfusion. But whether it is related to the protection of astrocytes and maintenance of the integrity of the blood-brain barrier in VD model remains unclear. This study will focus on the signal pathway by which σ1R affect the blood-brain barrier, and the regulating mechanism of astrocytes in the global cerebral ischemia-reperfusion mice model using σ1R-specific agonists, antagonists, and σ1R knockout mice.

英文关键词： sigma-1 receptor;vascular dementia;blood brain barrier;astrocyte;learning and memory