Dexmedetomidine reduces acute lung injury caused by LPS through the SIRT3 signaling pathway in vivo
Acute lung injury (ALI) is a clinical syndrome characterized by excessive inflammatory responses. Despite the exploration of various therapeutic approaches, no effective pharmacological treatment is currently available for ALI. In the current study, we investigated the role of SIRT3 in LPS-induced A...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1524219/full |
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| author | Jian Chen Jian Chen Jian Chen Yang Cai Yang Cai Yang Cai Xiaochun Peng Xiaochun Peng Xiaochun Peng Yuanling Xu Yuanling Xu Yuanling Xu Liying Chen Liying Chen Liying Chen Xinxin Pan Xinxin Pan Xinxin Pan Yingying Sun Yingying Sun Yingying Sun |
| author_facet | Jian Chen Jian Chen Jian Chen Yang Cai Yang Cai Yang Cai Xiaochun Peng Xiaochun Peng Xiaochun Peng Yuanling Xu Yuanling Xu Yuanling Xu Liying Chen Liying Chen Liying Chen Xinxin Pan Xinxin Pan Xinxin Pan Yingying Sun Yingying Sun Yingying Sun |
| author_sort | Jian Chen |
| collection | DOAJ |
| description | Acute lung injury (ALI) is a clinical syndrome characterized by excessive inflammatory responses. Despite the exploration of various therapeutic approaches, no effective pharmacological treatment is currently available for ALI. In the current study, we investigated the role of SIRT3 in LPS-induced ALI and the potential protective effects of dexmedetomidine (Dex), an agent that activates α2-adrenergic receptors. Histological analysis showed extensive lung damage and increased inflammatory cells in LPS-treated lung samples, with elevated TUNEL+ cells indicating apoptosis (p < 0.05). SIRT3 mRNA and protein expression were significantly downregulated following LPS treatment, both in vivo and in vitro (p < 0.05). DEX administration restored protein SIRT3 levels and reduced inflammation, while the SIRT3 inhibitor 3-TYP negated these benefits (p < 0.05). Additionally, DEX reduced pro-inflammatory cytokine levels and oxidative stress, effects that were also diminished by 3-TYP (p < 0.05). Our findings suggest that DEX exerts its protective effects against LPS-induced ALI via modulation of the SIRT3/LKB1/AMPK signaling pathway, highlighting the critical role of SIRT3 in inflammatory and oxidative stress responses in ALI. |
| format | Article |
| id | doaj-art-a80149615246482491d77f61b33de5b2 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-a80149615246482491d77f61b33de5b22025-08-20T03:32:23ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15242191524219Dexmedetomidine reduces acute lung injury caused by LPS through the SIRT3 signaling pathway in vivoJian Chen0Jian Chen1Jian Chen2Yang Cai3Yang Cai4Yang Cai5Xiaochun Peng6Xiaochun Peng7Xiaochun Peng8Yuanling Xu9Yuanling Xu10Yuanling Xu11Liying Chen12Liying Chen13Liying Chen14Xinxin Pan15Xinxin Pan16Xinxin Pan17Yingying Sun18Yingying Sun19Yingying Sun20Department of Anesthesiology, Anhui Provincial children’s Hospital, Anhui, ChinaThe Fifth Clinical Medical College of Anhui Medical University, Anhui, ChinaThe Children’s Medical Center of Anhui Medical University, Anhui, ChinaDepartment of Anesthesiology, Anhui Provincial children’s Hospital, Anhui, ChinaThe Fifth Clinical Medical College of Anhui Medical University, Anhui, ChinaThe Children’s Medical Center of Anhui Medical University, Anhui, ChinaDepartment of Anesthesiology, Anhui Provincial children’s Hospital, Anhui, ChinaThe Fifth Clinical Medical College of Anhui Medical University, Anhui, ChinaThe Children’s Medical Center of Anhui Medical University, Anhui, ChinaDepartment of Anesthesiology, Anhui Provincial children’s Hospital, Anhui, ChinaThe Fifth Clinical Medical College of Anhui Medical University, Anhui, ChinaThe Children’s Medical Center of Anhui Medical University, Anhui, ChinaDepartment of Anesthesiology, Anhui Provincial children’s Hospital, Anhui, ChinaThe Fifth Clinical Medical College of Anhui Medical University, Anhui, ChinaThe Children’s Medical Center of Anhui Medical University, Anhui, ChinaDepartment of Anesthesiology, Anhui Provincial children’s Hospital, Anhui, ChinaThe Fifth Clinical Medical College of Anhui Medical University, Anhui, ChinaThe Children’s Medical Center of Anhui Medical University, Anhui, ChinaDepartment of Anesthesiology, Anhui Provincial children’s Hospital, Anhui, ChinaThe Fifth Clinical Medical College of Anhui Medical University, Anhui, ChinaThe Children’s Medical Center of Anhui Medical University, Anhui, ChinaAcute lung injury (ALI) is a clinical syndrome characterized by excessive inflammatory responses. Despite the exploration of various therapeutic approaches, no effective pharmacological treatment is currently available for ALI. In the current study, we investigated the role of SIRT3 in LPS-induced ALI and the potential protective effects of dexmedetomidine (Dex), an agent that activates α2-adrenergic receptors. Histological analysis showed extensive lung damage and increased inflammatory cells in LPS-treated lung samples, with elevated TUNEL+ cells indicating apoptosis (p < 0.05). SIRT3 mRNA and protein expression were significantly downregulated following LPS treatment, both in vivo and in vitro (p < 0.05). DEX administration restored protein SIRT3 levels and reduced inflammation, while the SIRT3 inhibitor 3-TYP negated these benefits (p < 0.05). Additionally, DEX reduced pro-inflammatory cytokine levels and oxidative stress, effects that were also diminished by 3-TYP (p < 0.05). Our findings suggest that DEX exerts its protective effects against LPS-induced ALI via modulation of the SIRT3/LKB1/AMPK signaling pathway, highlighting the critical role of SIRT3 in inflammatory and oxidative stress responses in ALI.https://www.frontiersin.org/articles/10.3389/fphar.2025.1524219/fullacute lung injurysirt3dexmedetomidineinflammationoxidative stress |
| spellingShingle | Jian Chen Jian Chen Jian Chen Yang Cai Yang Cai Yang Cai Xiaochun Peng Xiaochun Peng Xiaochun Peng Yuanling Xu Yuanling Xu Yuanling Xu Liying Chen Liying Chen Liying Chen Xinxin Pan Xinxin Pan Xinxin Pan Yingying Sun Yingying Sun Yingying Sun Dexmedetomidine reduces acute lung injury caused by LPS through the SIRT3 signaling pathway in vivo Frontiers in Pharmacology acute lung injury sirt3 dexmedetomidine inflammation oxidative stress |
| title | Dexmedetomidine reduces acute lung injury caused by LPS through the SIRT3 signaling pathway in vivo |
| title_full | Dexmedetomidine reduces acute lung injury caused by LPS through the SIRT3 signaling pathway in vivo |
| title_fullStr | Dexmedetomidine reduces acute lung injury caused by LPS through the SIRT3 signaling pathway in vivo |
| title_full_unstemmed | Dexmedetomidine reduces acute lung injury caused by LPS through the SIRT3 signaling pathway in vivo |
| title_short | Dexmedetomidine reduces acute lung injury caused by LPS through the SIRT3 signaling pathway in vivo |
| title_sort | dexmedetomidine reduces acute lung injury caused by lps through the sirt3 signaling pathway in vivo |
| topic | acute lung injury sirt3 dexmedetomidine inflammation oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1524219/full |
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