Kaempferol improves periventricular white matter injury in premature infants by inhibiting microglial activation

Abstract

This study mainly explored the mechanism by which kaempferol inhibits the activation of microglia, thereby improving periventricular white matter injury (WMI) in premature infants. Firstly, WMI model of premature rats was herein established and assigned into WMI model group, kaempferol group, hypoxia-inducible factor 1 (HIF-1) group and kaempferol group+HIF-1 group. Four pups were taken from each group for swimming test and open field test to detect the behavioral function. hematoxylin-eosin staining (HE) staining assessed lateral ventricles along with expressions of HIF-1α gene and protein related to myelination and activation of microglial cells. Kaempferol promoted the recovery of early motor function after WMI around the pups through the HIF-1 pathway. Compared with WMI model group, kaempferol group, HIF-1 group, and kaempferol group+HIF-1 group rats had significantly reduced lateral ventricle area after drug intervention, especially in the kaempferol group+HIF-1 group, where it was decreased most significantly (all P <0.05). Moreover, Kaempferol reduced the expression of HIF-1α and had an effect on mRNA expression of myelin-related genes [Myelin basic protein (MBP) Multiepitope antigenic gene (MAG), myelin oligodendrocyte glycoprotein (MOG) and Recombinant Early Growth Response Protein 1 (EGR1) in the brain tissue of offspring rats. The number of activated microglial cells in the cingulate gyrus and corpus callosum of WMI model group were significantly increased and reduced after drug intervention, especially in the kaempferol group+HIF-1 group (P <0.05). Kaempferol reduced HIF-1α expression by inhibiting HIF-1 pathway, so as to inhibit microglial cell activation, which is related to its significant anti-inflammatory and anti-oxidative pharmacological mechanism with promising brain protection effect, which provides a new direction for drug treatment of WMI.