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Am J Perinatol 2024; 41(08): 1039-1049
DOI: 10.1055/a-1787-3396
Original Article

Resveratrol Attenuates Hyperoxia Lung Injury in Neonatal Rats by Activating SIRT1/PGC-1α Signaling Pathway

Kun Yang
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Menghan Yang 
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Yunchuan Shen 
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Lan Kang
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Xiaodan Zhu
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Wenbin Dong
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
,
Xiaoping Lei
1   Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China
2   Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
3   Sichuan Clinical Research Center for Birth Defects, Luzhou, China
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Funding This article was supported by the National Natural Science Foundation of China (81571480), Sichuan Science and Technology Department Major Science and Technology Special Project (22ZDYF1470), and Luzhou Municipal People's Government-Southwest Medical University Science and Technology Strategic Cooperation Project (2020LZXNYDJ03)
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Abstract

Objectives Our previous study showed that resveratrol (Res) attenuates apoptosis and mitochondrial dysfunction in alveolar epithelial cell injury induced by hyperoxia by activating the SIRT1/PGC-1α signaling pathway. In the present study, we investigated whether Res protects against hyperoxia-induced lung injury in neonatal rats by activating SIRT1/PGC-1α signaling pathway.

Methods Naturally delivered neonatal rats were randomly divided into six groups: normoxia + normal saline, normoxia + dimethyl sulfoxide (DMSO), normoxia + Res, hyperoxia + normal saline, hyperoxia + DMSO, and hyperoxia + Res. Lung tissue samples were collected on postnatal days 1, 7, and 14. Hematoxylin and eosin staining was used to evaluate lung development. Dual-immunofluorescence staining, real-time polymerase chain reaction, and western blotting were used to evaluate the levels of silencing information regulator 2-related enzyme 1 (SIRT1), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), nuclear respiratory factor 1 (Nrf1), Nrf2, transcription factor A (TFAM) and citrate synthase, the number of mitochondrial DNA (mtDNA) and mitochondria, the integrity of mtDNA, and the expression of TFAM in mitochondria.

Results We found that hyperoxia insulted lung development, whereas Res attenuated the hyperoxia lung injury. Res significantly upregulated the levels of SIRT1, PGC-1α, Nrf1, Nrf2, TFAM, and citrate synthase; promoted TFAM expression in the mitochondria; and increased the copy number of ND1 and the ratio of ND4/ND1.

Conclusion Our data suggest that Res attenuates hyperoxia-induced lung injury in neonatal rats, and this was achieved, in part, by activating the SIRT1/PGC-1α signaling pathway to promote mitochondrial biogenesis.

Key Points

  • Hyperoxia insulted lung development in neonatal rats.

  • Resveratrol promoted mitochondrial biogenesis to attenuate hyperoxia lung injury in neonatal rats.

  • Resveratrol, at least in part, promoted mitochondrial biogenesis by activating the SIRT1/PGC-1α signaling pathway.

Keywords

bronchopulmonary dysplasia - resveratrol - SIRT1 - PGC-1α - mitochondrial biogenesis


Publikationsverlauf

Eingereicht: 15. Dezember 2021

Angenommen: 24. Februar 2022

Accepted Manuscript online:
03. März 2022

Artikel online veröffentlicht:
12. Mai 2022

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