羟脯氨酸通过调节自噬和抗衰老表达来减轻LPS诱导的小鼠急性肺损伤

Title:Hydroxytyrosol Attenuates LPS-Induced Acute Lung Injury in Mice by Regulating Autophagy and Sirtuin Expression

Volume: 17 Issue: 2

关键词: 羟脯氨酸，脂多糖，自噬，抗衰老，急性肺损伤，呼吸窘迫综合征

摘要: Background: Recently, the effects of hydroxytyrosol on autophagy during acute lung injury (ALI) have drawn increasing attention.

Objective: We explored the underlying molecular mechanisms by which hydroxytyrosol exerts its anti-inflammatory effects in a murine model of ALI by up-regulating autophagy.

Methods: Male BALB/c mice, challenged with intranasal instillations of LPS, were treated with or without hydroxytyrosol (HT, 100 mg/kg, intragastrically) 1 h prior to LPS exposure. Twenty-four hours later, lung and bronchoalveolar lavage (BAL) fluid samples were obtained for the determination of lung wet to dry weight (W/D) ratios, protein leakage levels, and differential counts of inflammatory cells in BAL fluid. LPS-induced cytokine activity, inflammatory factor levels, sirtuin (SIRT1/3/6) expression, mitogenactivated protein kinase (MAPK) activation, and autophagy marker expression in ALImice were examined by western blotting and staining methods. Molecular docking between HT and SIRT and MAPK was studied with a Sybyl/Surflex module.

Results: LPS-stimulated SIRT inhibition, MAPK phosphorylation, and autophagy suppression were all notably abolished by HT administration. HT treatment significantly attenuated pulmonary edema and inflammatory cell infiltration into lung tissues, accompanied by decreased lung W/D ratios, protein concentrations, and inflammatory cell levels in BAL fluid. LPS driven release of inflammatory mediators, including TNF-α, IL-1β, IL-6, IL-10, and MCP-1, was strongly regulated by HT.

Conclusions: The protective effect of HT on lung inflammation in ALI mice may be attributed to the promotion of autophagy, which is likely associated with the activation of the SIRT/MAPK signaling pathway. Importantly, this study provides new insight into the molecular mechanisms of HT and its therapeutic potential in the treatment of acute respiratory distress syndrome.

Cite this article as:

Hydroxytyrosol Attenuates LPS-Induced Acute Lung Injury in Mice by Regulating Autophagy and Sirtuin Expression, Current Molecular Medicine 2017; 17 (2) . https://dx.doi.org/10.2174/1566524017666170421151940

DOI https://dx.doi.org/10.2174/1566524017666170421151940	Print ISSN 1566-5240
Publisher Name Bentham Science Publisher	Online ISSN 1875-5666