慢性脑低灌注（CCH）与多种缺血性脑血管病的病理发生密切相关，临床上尚缺乏有效的干预措施，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。自噬是一把双刃剑，异常的自噬过程与神经细胞的各种损伤也密切相关。目前国内外关于颅内慢性缺血状态下自噬过程对神经细胞的影响尚缺乏深入研究，有限的研究结果也有较大的争议。本项目拟以整体动物为研究对象，从神经组织学、神经行为学、分子生物学等多维层面，考察在CCH状态下自噬过程对神经细胞的影响。此外，我们前期研究发现大麻素内源性配基失活系统化合物即脂肪酰胺水解酶抑制剂URB597可明显降低神经细胞凋亡及炎症反应，改善认知功能障碍，提示URB597这种抑制内源性大麻素失活系统的化合物具有一定的神经保护作用。本项目拟进一步考察URB597对慢性脑低灌注动物自噬过程的影响及相关机制，有助于发现药物干预的新靶点，为改善患者在CCH状态下神经功能损伤提供科学依据。

Chronic cerebral hypoperfusion (CCH),which is associated with several ischemic cerebrovascular diseases, may lead to cognitive impairment and social dysfunction in patients. It remains unknown how to prevent the cognitive deterioration associated with CCH clinically. Autophagy, the process of self-degradation of cellular components, is a double-edged sword. Abnormal autophagy process is associated with various kinds of neuronal damage. To our knowledge, the studies with respect to the impact of autophagy process on neuronal cells under chronic cerebral ischemia are scarce. Moreover, the effect of autophagy process in experimental models of cerebral ischemia is controversial. In this study, based on neuronal histology, neuronal behavior, molecular biology,etc, we try to investigate the effects of autophagy process on the neuronal cells under the condition of CCH. In addition, our previous studies demonstrated that treatment of URB597, a selective inhibitor of fatty acid amide hydrolyase (FAAH) for the degradation of endocannabinoid ligands, can reverse CCH-induced neuronal apoptosis,neuroinflammatory responses and cognitive deficits, indicating the neuroprotective effect of URB597. In this study, we further investigate the effect of URB597 on the autophagy process in rats with CCH and the potential mechanism underlying its action, which might enable us to find a novel strategy and provide the new evidence for the repair of ischemic neuronal damage.