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 (a kind 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 -2 administration 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 day1 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 day1) and secondary septa counts at postnatal day1 and 3, respectively (P=0.002, P=0.026) than LPS-induced model group, while mean linear intercept was the opposite situation at postnatal day1 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 Alox15 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 of APS-II -2 on inflammation.