Abstract: Objective    To explore the effect of rno-miR-161 on regulating egl-9 hypoxia-inducible factor 2(EGLN2) in frontal ferroptosis in vascular dementia (VD) rat.    Methods    Twenty-four adult male SD rats were randomly divided into a control group (sham), a model group (VD). The VD group was obtained by bilateral carotid artery ligation, while the sham group was not ligated with bilateral carotid artery. The Morris water maze test was applied to assess the symptoms of VD 4 weeks after surgery. RT-qPCR was used to detect the changes of rno-miR-161. RT-qPCR and Western blotting were used to detect the expression levels of EGLN2 and glutathione-dependent antioxidant enzyme glutathione peroxidase 4 (GPX4). The relationship between rno-miR-161 and EGLN2 was predicted by bioinformatics and luciferase reporter gene test. RT-qPCR and Western blotting were used to detect the effect of rno-miR-161-mimic and rno-miR-161-inhibitor on EGLN2 expression.  The expression of EGLN2 was interfered by interference technology and the expression of GPX4 was detected by Western blotting and RT-qPCR.   Results   Compared with the control group, the expression of rno-miR-161 was down-regulated in the frontal lobe, the EGLN2 expression was increased while GPX4 was down-regulated. The EGLN2 was the direct target of rno-miR-161. rno-miR-161-minic inhibited the expression of EGLN2, rno-miR-161-inhibitor resulted in higher EGLN2 expression. siEGLN2 promoted GPX4.   Conclusions    rno-miR-161 inhibits ferroptosis by targeting EGLN2 expression in VD rat model frontal lobe.

Key words: Vascular dementia,  ,  ,  , rno-miR-161,  ,  ,  , EGLN2,  ,  , Ferroptosis,  ,  ,  , GPX4