1. Protective effects of icariin-mediated SIRT1/FOXO3 signaling pathway on intestinal ischemia/reperfusion-induced acute lung injury.
- Author
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Zhang F, Li ZL, Xu XM, Hu Y, Yao JH, Xu W, Jing HR, Wang S, Ning SL, and Tian XF
- Subjects
- Acute Lung Injury pathology, Animals, Apoptosis drug effects, Apoptosis genetics, Apoptosis Regulatory Proteins metabolism, Bcl-2-Like Protein 11, Cytokines blood, Disease Models, Animal, Forkhead Box Protein O3, Glutathione metabolism, Glutathione Peroxidase metabolism, Intestines pathology, Male, Malondialdehyde metabolism, Membrane Proteins metabolism, Oxidative Stress drug effects, Oxidative Stress genetics, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Rats, Superoxide Dismutase metabolism, Acute Lung Injury etiology, Acute Lung Injury metabolism, Flavonoids pharmacology, Forkhead Transcription Factors metabolism, Intestinal Mucosa metabolism, Intestines blood supply, Reperfusion Injury complications, Signal Transduction drug effects, Sirtuin 1 metabolism
- Abstract
Acute lung injury (ALI) is a common complication following intestinal ischemia/reperfusion (I/R) and is a major contributing factor to its high mortality rate. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, has been reported to have an important role in apoptosis inhibition, oxidative stress resistance and cell lifespan extension through its deacetylation of forkhead box protein O3 (FOXO3). It has been demonstrated that icariin (ICA), a flavonoid extracted from Epimedium, upregulates SIRT1 expression. The aim of the present study was to examine whether ICA-mediated SIRT1/FOXO3 signaling pathway activation had a protective effect on intestinal I/R-induced ALI. The effects of ICA on intestinal I/R-induced ALI and its regulation of the SIRT1/FOXO3 signaling pathway on intestinal I/R-induced ALI were investigated in rats. The results demonstrated that ICA pretreatment markedly reduced intestinal I/R-induced ALI as indicated by histological alterations, including decreased tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), reduced oxidative stress, acetylated FOXO3 and B-cell lymphoma 2 (Bcl-2)-interacting mediator of cell death levels, and increased glutathione (GSH), GSH peroxidase, SIRT1, manganese superoxide dismutase and Bcl-2 levels in rat lung tissues. Furthermore, ICA pretreatment upregulated SIRT1 expression, which then downregulated FOXO3 acetylation. In conclusion, ICA exhibited significant protective effects in intestinal I/R-induced ALI. The protective effect of ICA may be attributed to the upregulation of SIRT1, which contributed to FOXO3 deacetylation and the modulation of downstream antioxidative and anti-apoptotic factors.
- Published
- 2015
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