To investigate the role and molecular mechanism of miRNA-210 regulating hypoxia inducible factor-1α (HIF-1α) expression in vascular cognitive impairment (VCI).

60 male 220-250 g rats were randomly divided into Sham operation group (Sham), Vascular cognitive impairment (VCI), Vascular cognitive impairment + miRNA-210 mimics group (VCI+miRNA-210 mimic) and Vascular cognitive impairment + mimics control group (VCI+ mimic control). The rat model of vascular cognitive impairment was established by four - vessel method. In order to up-regulated the expression of miRNA-210, the miRNA-210 mimic was injected into lateral ventricles. Morris water maze was used to evaluate the learning and memory ability of rats in each group on day 7,14 and 30 after VCI. The expression of miRNA-210 in the hippocampus was detected by qPCR.Western blotting was used to detect the expression levels of HIF-1α and NF-kB. The concentration of TNF-α in the hippocampus was detected by ELISA. The 3' untranslated region (3'UTR) dual luciferase reporter gene vector of HIF-1α was constructed to verify the molecular mechanism of miRNA-210 regulating HIF-1α. T test or Dunnett's T3 method were used to compare the differences among groups.

In VCI group, the cognitive impairment occurred, which the mean escape latency at 7, 14 and 30 days was significantly increased and the times of crossing the original platform was significantly decreased (P＜0.05). Compared with Sham group, the expressions of HIF-1α and NF-κB in the hippocampus of VCI group and VCI+miRNA-210 NC group were increased, and the release of inflammatory factor TNF-α was increased, with statistical significance（P＜0.05）. After injected miRNA-210 mimics into lateral ventricles, primary hippocampal cells were isolated.The activity of luciferase was significantly decreased in the co-transfected with miRNA-210 and wild-type HIF-1α 3’UTR group suggesting a target relationship between miRNA-210 and HIF-1α.

MiRNA-210 can improve vascular cognitive impairment in rats by reducing inflammation in the hippocampus, and the mechanism may be related to the down-regulation of HIF-1α expression.