Department of Anaesthesiology, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Affiliated Central Hospital of Huzhou University, No.1558 Sanhuan North Road, Huzhou City, Zhejiang Province, China.
Department of Radiology, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, No.315, South Street, Wuxing District, Huzhou City, Zhejiang Province, China.
Biomed Pharmacother. 2023 Sep;165:115018. doi: 10.1016/j.biopha.2023.115018. Epub 2023 Jun 17.
Acute lung injury (ALI) is an intractable medical problem linked with to high morbidity and mortality all over the worldglobally. The prognosis of advanced acute lung injury remains persistently poor due to its underlying mechanisms remain unclear.Despite advancements in medical research, the its prognosis of advanced ALI remains persistently poor due to unclear underlying mechanisms. We aimed to investigate the protective effects of silencing information regulator 1 (SIRT1) on lipopolysaccharide (LPS)-induced acute lung injuryALI and to reveal its underlying molecular mechanism.
Male Sprague--Dawley rats were divided grouped into 4 groupsfour: normal saline group (group NS), lipopolysaccharide group (group L), SIRT1 activator SRT1720-pretreated group (group S), and SIRT1 inhibitor EX527- pretreated group (group E). Rats They were intranasally dripped with LPS to establish the model of ALI modelsacute lung injury respectively. We investigated the effect of SIRT1 on acute lung injury by analysing We analyzed the CT images of the rat lungs and used, HE staining, lung wet-to-dry ratio, inflammatory factor expression, lung injury marker expression, immunohistochemistry, and related mRNA expression to determine the effect of SIRT1 on ALI.
Our results show that LPS induction produced resulted in acute lung injury, ALI and disrupting disrupted normal SIRT1 expression, which led to the overexpression of STAT3, TLR4, TNF-ɑ, and IL-6 and suppression of Cav-1 expression. Upregulation The upregulation of Cav-1 protein and mRNA following the administration of an SIRT1 agonist resulted in reduced lung injury. SRT1720 pretreatment was closely associated with reduced expressions of STAT3,TLR4, TNF-ɑ, and IL-6. ALI lung injury was more severeworsened after administration of SIRT1 inhibitors, and the changes in the above indicators were reversed.
These results suggest that SIRT1 may protect against LPS-induced acute lung injuryALI via by counteracting inflammatory remissionion, and this protective effect might may be mediated by suppressing STAT3 to activate the expression ofinduce Cav-1 expression.
急性肺损伤（ALI）是一种全球范围内发病率和死亡率都很高的棘手医学问题。由于其潜在机制尚不清楚，晚期急性肺损伤的预后仍然很差。尽管医学研究取得了进展，但由于潜在机制不清楚，晚期 ALI 的预后仍然很差。我们旨在研究沉默信息调节因子 1（SIRT1）对脂多糖（LPS）诱导的急性肺损伤（ALI）的保护作用，并揭示其潜在的分子机制。
雄性 Sprague-Dawley 大鼠分为 4 组：生理盐水组（NS 组）、脂多糖组（L 组）、SIRT1 激活剂 SRT1720 预处理组（S 组）和 SIRT1 抑制剂 EX527 预处理组（E 组）。分别用 LPS 滴鼻建立 ALI 模型。通过分析大鼠肺部 CT 图像、HE 染色、肺湿重干重比、炎症因子表达、肺损伤标志物表达、免疫组化及相关 mRNA 表达，研究 SIRT1 对 ALI 的影响。
我们的结果表明，LPS 诱导产生急性肺损伤，破坏 SIRT1 的正常表达，导致 STAT3、TLR4、TNF-ɑ和 IL-6 过表达，Cav-1 表达受抑制。给予 SIRT1 激动剂后，Cav-1 蛋白和 mRNA 上调，肺损伤减轻。SRT1720 预处理与 STAT3、TLR4、TNF-ɑ和 IL-6 的表达减少密切相关。给予 SIRT1 抑制剂后，ALI 肺损伤加重，上述指标变化逆转。
这些结果表明，SIRT1 可能通过抑制炎症反应来保护 LPS 诱导的急性肺损伤（ALI），这种保护作用可能是通过抑制 STAT3 激活 Cav-1 表达来介导的。
