Journal of Shanghai Jiao Tong University (Medical Science) ›› 2023, Vol. 43 ›› Issue (2): 171-179.doi: 10.3969/j.issn.1674-8115.2023.02.005

• Basic research • Previous Articles    

Improvement of alveolarization arrest in newborn rats with bronchopulmonary dysplasia via inhibiting alveolar epithelial cell pyroptosis

ZHENG Xiaoyan1(), WANG Xingyun2, ZHANG Yongjun1()   

  1. 1.Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
    2.Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
  • Received:2022-11-09 Accepted:2023-02-06 Online:2023-02-28 Published:2023-02-28
  • Contact: ZHANG Yongjun;


Objective ·To study the effect of gasdermin D (GSDMD) inhibitor necrosulfonamide (NSA) on alveolarization arrest in lipopolysaccharide (LPS)-induced bronchopulmonary dysplasia (BPD) newborn rats via inhibiting alveolar epithelial cell pyroptosis. Methods ·Pregnant SD rats were randomly assigned to four groups as follows: control, BPD, BPD with NSA and NSA group, and then were prepared to receive intra-amniotic injection of LPS. Lung tissues of newborn rats on the first, third and seventh day after birth were stained by hematoxylin-eosin (H-E) to observe lung development. The expressions of GSDMD-N-terminal in lungs of newborn rats in each group were detected by immunofluorescence. The mRNA levels of interleukin-1β (IL-1β) of newborn rats' lungs was detected by real-time PCR. In vitro, the mouse alveolar epithelial cell line MLE-12 was cultured and treated with LPS/adenosine triphosphate (ATP) and NSA. The cell viability of MLE-12 cells was detected by CCK-8 method, the pyroptosis was detected by Hoechst 33342 and propidium iodide (PI) staining, and the expressions of surfactant protein C (SFTPC) and GSDMD-N protein in MLE-12 cells were detected by immunofluorescence. Results ·In vivo, intra-amniotic injection of LPS hindered lung development, resulting in the pathological hallmarks of BPD. The GSDMD-N expression of alveolar epithelial cells increased in the BPD rat model established by intra-amniotic injection of LPS, while NSA treatment significantly improved the lung development of BPD rats and inhibited the IL-1β mRNA expression (both P<0.05). In vitro, the study confirmed that LPS/ATP treatment decreased the viability of alveolar epithelial cells MLE-12 and induced pyroptosis, while NSA treatment increased alveolar epithelial cell viability and inhibited pyroptosis (both P<0.05). In addition, NSA treatment upregulated the SFTPC expression and inhibited the GSDMD-N expression in LPS/ATP-stimulated alveolar epithelial cells (both P<0.05). Conclusion ·Inhibiting the alveolar epithelial cell pyroptosis can improve the alveolar development in BPD newborn rats.

Key words: bronchopulmonary dysplasia, pyroptosis, gasdermin D (GSDMD), alveolar epithelial cell

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