RESUMO
Objective: To investigate whether batyl alcohol (BTA) can improve the pathology of bronchopulmonary dysplasia (BPD) in newborn rats induced by lipopolysaccharide (LPS) and the mechanism. Methods: Pregnant SD rats (16.5 d) were randomly assigned into Saline group, LPS group, and LPS+BTA group. Amniocentesis injection of LPS was performed to establish neonatal bronchopulmonary dysplasia (BPD) rat model. In LPS+BTA group, LPS and BTA were injected at the same time. After birth, LPS+BTA group was injected with BTA continuously everyday for 7 days. The other two groups were injected with normal saline of equal volume. Lung tissues of neonatal rats on the first, third and seventh day after birth were stained by hematoxylin-eosin (H-E) and resorcin-fuchsin respectively, to observe alveolarization arrest. The mRNA and protein levels of interleukin 1β (IL-1β) in newborn rats lungs were detected by real-time PCR and ELISA. In vitro, mouse macrophages RAW264.7 were cultured to detect IL-1β mRNA levels and protein levels after treatment with LPS and BTA. SD rat bone marrow macrophages were isolated and treated with LPS and BTA. RNA-sequence was taken to screen for possible targets of BTA inhibition of inflammation. Results: The results of H-E staining showed that LPS+BTA group had a milder pathology of BPD, with more secondary septa counts, more alveolar counts, and smaller mean linear intercept (all P<0.05); after BTA intervention the expression levels of IL-1β mRNA and protein in lung tissues of neonatal rats were significantly lower than those in LPS group (both P<0.05). In vitro, IL-1β mRNA and protein increased after LPS stimulation (both P=0.000), but decreased in the LPS+BTA group (both P<0.05). RNA-sequence results showed that BTA inhibited the expressions of some inflammatory factors, such as thrombospondin1 (Thbs1), triggering receptor expressed on myeloid cells 1 (Trem1), and cluster of differentiation 274 (Cd274), and promoted the expressions of some anti-inflammatory factors, such as complement C1q C chain (C1qc), RT1 class Ⅱ, locus Da (RT1-Da), and RT1 class Ⅱ, locus Db1 (RT1-Db1). Conclusion: BTA can improve lung pathology of neonatal rats with BPD by downregulating the expression of IL-1β and reducing inflammatory response.