Overexpression of miR-199a-5p improves brain injury in newborn rats with intrauterine infection via inhibition of astrocyte activation

Abstract

White matter injury is the most common form of brain injury in preterm infants. In addition to hypoxia ischemia, intrauterine infection is most closely related to brain white matter injury. Our study aimed to explore the mechanism of the miR-199a-5p/HIF-1α axis on astrocyte activation and brain injury in newborn rats caused by intrauterine infection.The animal/cell model was established via escherichia coli infection/lipopolysaccharide induction, followed by the measurement of body weight, brain weight, and the pathological changes in brain tissues of newborn rats, and the pathological changes in placenta and uterus wall of pregnant rats. Also, the levels of GFAP, TNF-α, MDA, GSH, SOD, miR-199a-5p, and HIF-1α were detected though corresponding assays or kits. In vitro, cell viability and apoptosis and the levels of IL-6 and TNF-α were evaluated in astrocytes. Moreover, the targeting relationship between miR-199a-5p and HIF-1α was verified.miR-199a-5p was lowly expressed in the brain tissues of newborn rats with intrauterine infection. Overexpression of miR-199a-5p relieved the injury of placenta and uterus wall in pregnant rats and brain injury in newborn rats, accompanied by decreased HIF-1α, GFAP, TNF-α, and MDA levels and increased GSH and SOD levels. Results from cell models showed that miR-199a-5p overexpression inhibited astrocyte activation, shown by enhanced cell viability, weakened cell apoptosis, and decreased GFAP, IL-6, and TNF-α. Mechanistically, miR-199a-5p targeted HIF-1α to decrease its expression.Collectively, miR-199a-5p inhibited astrocyte activation and alleviated brain injury in newborn rats with intrauterine infection by reducing HIF-1α expression.