Effect of APS-Ⅱ-2 on intra-amniotic lipopolysaccharide-induced alveolarization arrest in bronchopulmonary dysplasia model rats / 上海交通大学学报（医学版）

ABSTRACT

Objective·To investigate the role of APS-Ⅱ-2 (akind of plant-derived natural drug)on amelioration of chorioamnionitis-induced alveolarization arrest and the underlying mechanism.Methods·Bronchopulmonary dysplasia (BPD) model was constructed by intra-amniotic injection of lipopolysaccharide (LPS) in SD rats (E16.5).The SD rats were randomly divided into control group (Saline group)、LPS model group (LPS+Saline group) and APS-Ⅱ-2administration group (LPS+APS-Ⅱ-2 group).Then neonatal rats in LPS+APS-Ⅱ-2 group were given an intraperitoneal injection with APS-Ⅱ-2 (50 mg/kg) for 3 consecutive days after birth,whereas rats in LPS+Saline group and Saline group were administrated with an equal amount of normal saline.To examine pathologic change of pulmonary in neonatal rats,hematoxylin-eosin (H-E) staining was performed at postnatal dayl and 3.Then bone marrowderived macrophages (BMDMs) from SD rats were detected by the technology of RNA-sequence to research the immunomodulation of APS-Ⅱ-2.Results·APS-Ⅱ-2 administration group had drastically higher terminal air spaces (P=0.033 at postnatal dayl) and secondary septa counts at postnatal dayl and 3,respectively (P=0.002,P=0.026) than LPS-induced model group,while mean linear intercept was the opposite situation at postnatal dayl and 3,respectively (P=0.006,P=0.004).The detection of RNA-sequence indicated that APS-Ⅱ-2 suppressed the expression of inflammatory cytokines such as Tlr3,Tlr7 and Tlr8 in BMDMs.Meanwhile,it also promoted some pleiotropic cytokines with anti-inflammatory effects such as Alox1 5 and Cd74.Conclusion·Administration of APS-Ⅱ-2 could improve the pathology of BPD,thereby supporting the ethnopharmacological uses of the plant.This effect may be directly caused by modulatory effects ofAPS-Ⅱ-2 on inflammation.