慢性低灌注在认知功能障碍性疾病发生发展过程中起着重要作用，但确切机制尚不完全清楚。已有研究表明miRNAs参与调控慢性低灌注所导致的认知功能障碍。我们前期研究发现在大鼠慢性低灌注模型（2VO）的脑组织以及血管性痴呆患者脑脊液和血液中miR-128的表达明显下降，外源性给予miR-128的激动剂逆转miR-128的表达可有效逆转2VO大鼠的认知功能障碍。并且，我们成功鉴定出miR-128直接调控下游靶基因TROVE2（凋亡调控蛋白）的表达。基于以上研究，我们推测在慢性低灌注脑中，下调的miR-128可能会引起TROVE2蛋白的高表达，并通过其下游信号通路介导了细胞凋亡，促发了认知功能障碍。我们拟在PC12细胞和2VO动物模型中，利用行为学、分子生物学等技术，明确miR-128/TROVE2在慢性低灌注所致认知障碍中的作用和机制，为痴呆类疾病的早期防治提供新线索。

Chronic hypoperfusion plays an important role in the process of cognitive dysfunction, but the exact mechanism is not fully clear. Previous studies have shown that miRNAs involved in cognitive dysfunction caused by chronic hypoperfusion. Our previous study found that the level of miR-128 are dramatically decreased in chronic hypoperfusion rat models and vascular dementia patients, exogenous agomer of miR-128 can effectively improve the congnitive dysfunction in 2VO animals. Otherwise, we successfully identified miR-128 regulate the target gene TROVE2 (apoptosis-related protein). Based on our previous study, we hypothesized that the decrease level of miR-128 resulted in up-regulation of TROVE2, and neuronal apoptosis mediated by the miR-128/TROVE2 signaling pathway could lead to the cognitive dysfunction. We will use the molecular biology and behavior tests technology in PC12 cell lines and 2VO models, to determine the mechanism of miR-128/TROVE2 in cognitive dysfunction caused by chronic hypoperfusion, which will provide new clues for the prevention and treatment of dementia diseases.