LPS Induced Inflammation, Lung Maturation And BPD In Preterm Rats

Objective: To determine the effects of the increasing severity ofmaternal and fetal inflammation induced by various doses of intraamnioticLPS(Lipopolysaccharide) on lung maturation and development, andcompare these effects with DXM(dexamethasone) in preterm rats.Methods: Forty SD rats were randomly assigned to Blank(n=4),NS(Sterile saline, n=4), L0.05, L0.25, L2, L8, L10(doses of LPS, μg/sac，n=5,5,5,5,7, respectively) and DXM (50μg/sac, n=5) groups. Intraamnioticinjections performed on G19.48h later, chorioamnionitis, fetal lunginflammation and umbilical vasculitis were observed and scored. SP-A,SP-B, SP-C (Surfactant protein A,B,C), FGF-7(Fibroblast growth factor),IL-1β, TNF-α mRNAs in lung and IL-1β, TNF-α mRNAs in chorioamnionwere determined by qRT-PCR. FGF-7protein expression in lung wasexamined by immunohistochemistry. Effects on lung development wereassessed by morphologic observation on P3, P15(Postnatal day3,15) andpulmonary function test on P15.Results: Scores of chorioamnionitis, fetal lung inflammation andumbilical vasculitis increased in a dose-dependent way from0.25to10μg/sac LPS.0.25and2μg/sac induced an increase in IL-1β and TNF-αmRNAs in lung and chorioamnion, accompany with lung maturation whichindicated by increased SP-A, SP-B, SP-C mRNAs, but did not alter lungmorphology on P3, P15and neither caused dysfunction of pulmonaryventilation on P15.8μg/sac attenuated surfactant synthesis and delayed morphological maturation of lung.10μg/sac directly undermined normallung structure. Moderate inflammation induced by LPS upregulated FGF-7mRNA and protein in fetal lung.Conclusion: There was a clear dose–response relationship betweenintraamniotic LPS and prenatal inflammation. Mild to moderatechorioamnionitis, fetal lung inflammation and umbilical vasculitis improvedlung maturation without increasing the susceptibility for subsequentBPD(Bronchopulmonary dysplasia) in rats. IL-1β, TNF-α and FGF-7mightplay roles in this process.