慢性脑低灌注可诱导神经细胞变性，是导致患者认知功能障碍和社会行为能力低下的重要因素，与多种神经变性性脑血管疾病的病理发生有着密切关系，临床上尚缺乏有效的干预措施。内源性大麻素系统（ECS）包括G蛋白耦联受体CB1、CB2，内源性配基AEA、2-AG及其内源性配基失活系统AEA水解酶FAAH等，研究表明，ECS在中枢神经系统具有多种内源性生理性调节作用并介导哺乳动物的神经保护作用。我们前期研究发现慢性脑低灌注可诱导SD大鼠海马组织中CB1受体表达水平明显降低，提示ECS功能异常。本项目拟以整体动物为研究对象，从ECS的受体水平、失活系统和免疫应答（小胶质细胞反应）等多维层面考察慢性脑低灌注对大鼠认知功能障碍影响的关键环节及其调控机制，有助于发现新的药物干预作用靶点，为改善患者的认知功能提供科学依据。

Chronic cerebral hypoperfusion (CCH) may lead to neurodegeneration and paly an important role in the cognitive impairment and dysfunction of the patient's social behavior. This pathophysiological procedure usually occurs in various kinds of cerebral vascular diseases with special respect to the neurodegeneration. It remains unknown how to prevent the cognitive deficit associated with CCH clinically. The endocannabinoid system (ECS) consists of the G protein coupled receptors CB1 and CB2, the endogenous ligands anandamid (AEA) and 2-arachidonylglycerol (2-AG), and the endocannabinoid-inactivating enzyme fatty acid amide hydrolase (FAAH). It has been shown that the ECS implicated in the endogenous regulation of different physiological functions in the central nervous system and the neuroprotective effects in the mammals. Our previous study demonstrated that CCH can result in the decrease of neuronal cannabinoid CB1 receptor expression in the hippocampal tissues in SD rats, suggesting the dysfunction of the ECS. In this study, we will investigate the key roles of CCH on the cognitive impairment and its regulation mechanisms in rats based on the receptor levels of the ECS, inactivity system and immune response (microglial activation). The study will enable us to find a new drug target and provide scientific evidence for improving the patient's cognitive function.