关键词: 长期脑低灌注, 痴呆, miR-195, 淀粉样多肽级联反应

Abstract: Chronic brain hypoperfusion （CBH） is a common clinical manifestation of vascular dementia （VD）. Clarifying the effects of CBH on cognitive function would help to improve our understanding the pathophysiological mechanism of VD and provide the possible therapeutic strategy for VD. In recent years， our group focused on to investigate the action and molecular mechanisms of CBH on learning and memory ability of rats using a CBH model by bilateral common carotid artery occlusion （or called two-vessel occlusion，2VO）. We found that miR-195 could regulate cognitive ability of CBH rats through targeting on varies genes simultaneously that associated with all three pathological processes including amyloid β peptide （Aβ） deposition， tau hyperphosphorylation， dendritic degeneration and neuronal loss. Importantly，miR-195 could not only prevent the initial amyloidogenic cascade response via downregulating amyloid precursor protein （APP） and β-site APP cleaving enzyme 1 （BACE1）， but also provide sufficient requisite substrates during the amyloidogenic cascade response process. In addition，our series studies also provide evidence that miRNAs could participate in the onset and the development processes of diseases by regulating multi-targets within one functional module.

Key words: chronic brain hypoperfusion, dementia, microRNA-195, amyloidogenic cascade response