Intracerebroventricular Injection Of MiR-219 Agomir Improves Lipopolysaccharideinduced Impairment Of Oligodendrocyte Maturation In Newborn Rats

Background: Severe inflammatory response and bacteremia in are neonatal period are important risk factors for neonatal white matter injury,the machanisms of which are related to impairment of oligodendrocyte maturation.Oligodendrocytes are one of the cells that constitute central nervous system.miR-219 is an oligodendrocyte-specific miRNA.It is also the most expressed miRNA in differentiation of oligodendrocytes.Dugas found that miR-219 can promote OPCs differentiate to OLs in vitro experiments.miRNA-based therapy is the hot spot in the research of diseases treatment.It has been shown that intracerebroventricular injection of miRNA agonists or inhibitors has therapeutic effects on brain damage.However,the effct of miR-219 on inflammation-induced neonatal white matter injury is still unclear.Objective: To investigate the effect of intracerebroventricular injection of miR-219 agomir on lipopolysaccharide(LPS)-induced white matter injury in newborn rats.Methods:(1)Two-day-old Sprague-Dawley rats were randomly divided into 2 groups and subjected to intraperitoneal injections of normal saline or LPS(0.25 mg/kg).RT-qPCR was used to detect the expression of miR-219 and IL-1? mRNA in brain tissues.HE staining and nissl staining were used to observe the pathological changes of the white matter.(2)Two-day-old Sprague-Dawley rats were randomly divided into 4 groups and subjected to intraperitoneal injections of normal saline or LPS(0.25 mg/kg),followed 24 h later by intracerebroventricular injection of the negative control miR agomir or mi R-219 agomir.RT-q PCR was used to detect the expression of miR-219 and myelin basic protein(MBP)mRNA in brain tissues.Mature oligodendrocytes and OPCs were identified using immunofluorescence,and the expressions of MBP,PDGFR? and Sox6 proteins in the brain tissue were detected using Western blotting.Results:(1)Intraperitoneal injection of LPS resulted in significantly increased expressions of IL-1? mRNA in the brain tissue of the rats(P<0.05)and significantly reduced expressions of miR-219(P<0.05).Intraperitoneal injection of LPS caused obvious white matter injuries highlighted by loosened tissue structure,nuclear condensation and reduction of nissl bodies.(2)Intraperitoneal injection of LPS induced a significant decrease in the expression of MBP(the marker of mature oligodendrocytes)along with a significant decrease in the expression of PDGFR?(the marker of mature OPCs)and oligodendrocyte differentiation inhibitory factor Sox6(P<0.05).Intracerebroventricular injection of miR-219 agomir resulted in significantly increased expressions of miR-219 in the brain tissue of the rats(P<0.05).Compared with those in LPS + control miR agomir group,the rats in LPS + miR-219 group showed significantly increased MBP expression and decreased expression of PDGFR? and Sox6 in the brain tissue(P<0.05),and no significant differences were found in MBP,PDGFR? or Sox6 expressions between the saline + control miR agomir group and LPS + miR-219 group(P>0.05).Conclusion:(1)Intraperitoneal injection of LPS can lead to white matter injury in neonatal SD rats,and reduce the expression of miR-219.(2)Intraperitoneal injection of LPS can lead to impairment of oligodendrocyte maturation in neonatal SD rats.Intracerebroventricular injection of miR-219 can increase the expression of miR-219 and reduce the expression of sox6,thus improving LPS-induced impairment of oligodendrocyte maturation in newborn rats.