Chen Jian, Cai Yang, Peng Xiaochun, Xu Yuanling, Chen Liying, Pan Xinxin, Sun Yingying
Department of Anesthesiology, Anhui Provincial children's Hospital, Anhui, China.
The Fifth Clinical Medical College of Anhui Medical University, Anhui, China.
Front Pharmacol. 2025 Jun 25;16:1524219. doi: 10.3389/fphar.2025.1524219. eCollection 2025.
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 ( < 0.05). SIRT3 mRNA and protein expression were significantly downregulated following LPS treatment, both and ( < 0.05). DEX administration restored protein SIRT3 levels and reduced inflammation, while the SIRT3 inhibitor 3-TYP negated these benefits ( < 0.05). Additionally, DEX reduced pro-inflammatory cytokine levels and oxidative stress, effects that were also diminished by 3-TYP ( < 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.
急性肺损伤（ALI）是一种以过度炎症反应为特征的临床综合征。尽管对各种治疗方法进行了探索，但目前尚无针对ALI的有效药物治疗方法。在本研究中，我们研究了SIRT3在脂多糖（LPS）诱导的ALI中的作用以及右美托咪定（Dex）的潜在保护作用，右美托咪定是一种激活α2肾上腺素能受体的药物。组织学分析显示，LPS处理的肺样本中存在广泛的肺损伤和炎症细胞增多，TUNEL+细胞升高表明存在细胞凋亡（P<0.05）。LPS处理后，SIRT3 mRNA和蛋白表达均显著下调（P<0.05）。给予DEX可恢复SIRT3蛋白水平并减轻炎症，而SIRT3抑制剂3-TYP则消除了这些益处（P<0.05）。此外，DEX降低了促炎细胞因子水平和氧化应激，3-TYP也减弱了这些作用（P<0.05）。我们的研究结果表明，DEX通过调节SIRT3/LKB1/AMPK信号通路对LPS诱导的ALI发挥保护作用，突出了SIRT3在ALI炎症和氧化应激反应中的关键作用。
