Abstract
Purpose/Aim
Bronchopulmonary dysplasia (BPD) is associated with poor survival in preterm infants. Intrauterine infection can aggravate the degree of obstruction of alveolar development in premature infants; however, the pathogenic mechanism remains unclear. In this study, we sought to determine whether pyroptosis could be inhibited by downregulating mammalian target of rapamycin (mTOR) activation and inducing autophagy in BPD-affected lung tissue.
Materials and Methods
We established a neonatal rat model of BPD induced by intrauterine infection via intraperitoneally injecting pregnant rats with lipopolysaccharide (LPS). Subsequently, mTOR levels and pyroptosis were evaluated using immunohistochemistry, immunofluorescence, TUNEL staining, and western blotting. The Shapiro–Wilk test was employed to assess the normality of the experimental data. Unpaired t-tests were used to compare the means between two groups, and comparisons between multiple groups were performed using analysis of variance.
Results
Pyroptosis of lung epithelial cells increased in BPD lung tissues. After administering an mTOR phosphorylation inhibitor (rapamycin) to neonatal rats with BPD, the level of autophagy increased, while the expression of autophagy cargo adaptors, LC3 and p62, did not differ. Following rapamycin treatment, NLRP3, Pro-caspase-1, caspase-1, pro-IL-1β, IL-1β, IL-18/Pro-IL-18, N-GSDMD/GSDMD, Pro-caspase-11, and caspase-11 were negatively regulated in BPD lung tissues. The opposite results were observed after treatment with the autophagy inhibitor MHY1485, showing an increase in pyroptosis and a significant decrease in the number of alveoli in BPD.
Conclusions
Rapamycin reduces pyroptosis in neonatal rats with LPS-induced BPD by inhibiting mTOR phosphorylation and inducing autophagy; hence, it may represent a potential therapeutic for treating BPD.
Acknowledgments
We thank Editage for their assistance with English language editing.
Authors’ contributions
FZ conceptualized and designed the study, validated the data, analyzed and curated the data, performed the experiments, performed software-related analysis, and wrote and revised the manuscript. LL conceptualized the study, validated and curated the data, acquired funding, obtained resources, revised the manuscript, supervised the study, and performed visualization and administration of the project. MW, ZL, YF, ZG, YZ, and LH performed the experiments and wrote the original draft of the manuscript. JD performed the experiment and revised the manuscript. All authors read and approved the final manuscript.
Disclosure statement
The authors report there are no competing interests to declare.