Your browser doesn't support javascript.
loading
Rapamycin attenuates pyroptosis by suppressing mTOR phosphorylation and promoting autophagy in LPS-induced bronchopulmonary dysplasia.
Zhang, Feng; Wang, Minrong; Li, Zhongni; Deng, Jiehong; Fan, Yang; Gou, Zhixian; Zhou, Yue; Huang, Li; Lu, Liqun.
Afiliação
  • Zhang F; Department of Pediatrics, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China.
  • Wang M; Clinic Medical College, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China.
  • Li Z; Department of Pediatrics, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China.
  • Deng J; Clinic Medical College, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China.
  • Fan Y; Department of Pediatrics, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China.
  • Gou Z; Clinic Medical College, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China.
  • Zhou Y; Department of Pediatrics, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China.
  • Huang L; Clinic Medical College, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China.
  • Lu L; Department of Pediatrics, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China.
Exp Lung Res ; 49(1): 178-192, 2023.
Article em En | MEDLINE | ID: mdl-37874145
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-1ß, IL-1ß, 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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 6_ODS3_enfermedades_notrasmisibles / 7_ODS3_muertes_prevenibles_nacidos_ninos Base de dados: MEDLINE Assunto principal: Displasia Broncopulmonar Limite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Exp Lung Res Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 6_ODS3_enfermedades_notrasmisibles / 7_ODS3_muertes_prevenibles_nacidos_ninos Base de dados: MEDLINE Assunto principal: Displasia Broncopulmonar Limite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Exp Lung Res Ano de publicação: 2023 Tipo de documento: Article