Abstract
Neonatal hypoxic-ischemic brain damage (HIBD) is a common factor in neonatal fatalities. miR-126-3p content in cerebral hemorrhage patients is obviously decreased, but its mechanism of action in HIBD is still unclear. The HIBD model was constructed by Rice-Vannucci method, and the change in miR-126-3p was detected. The target genes of miR-126-3p were obtained by database (miRWalk, TargetScan, miRTarbase and miRDB) analysis. The targeting relationship between miR-126-3p and low density lipoprotein receptor related protein (LRP6) was explored based on a dual luciferase assay. miR-126-3p over- and lowexpressed, LRP6 overexpressed and protein kinase C (PKC) pathway agonist phorbol 12-myristate 13-acetate (PMA) were injected into the brains of neonatal rats. The pathological changes in cerebral tissue and neuronal survival were observed by pathological staining. The neurological function was evaluated by foot fault test and wire suspension test. The levels of interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) were tested by an ELISA kit. The levels of miR-126-3p, LRP6 and PKC/ERK pathway proteins were tested by qRT-PCR and Western blot. Knockdown of miR-126-3p can aggravate inflammation, brain tissue pathology and neurological impairment in HIBD, while miR-126-3p overexpression can improve it. miR-126-3p can target down-regulate LRP6. miR-126-3p can improve HIBD by down-regulating LRP6 expression and activating the PKC/ERK signaling pathway. miR-126-3p can target down-regulate LRP6 by activating the PKC/ERK signaling pathway to inhibit inflammation in HIBD rats, reduce brain tissue pathology and neurological damage, and improve HIBD. Key words miR-126-3p " LPR6 " PKC/ERK pathway " Hypoxic-ischemic brain damage.