Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310005, China.
Zhejiang Respiratory Drugs Research Laboratory, School of Basic Medical Sciences, Zhejiang University, Hangzhou, 310058, China.
Inflammation. 2018 Jun;41(3):1093-1103. doi: 10.1007/s10753-018-0761-3.
Quercetin (Que) as an abundant flavonol element possesses potent antioxidative properties and has protective effect in lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the specific mechanism is still unclear, so we investigated the effect of Que from in vivo and in vitro studies and the related mechanism of cAMP-PKA/Epac pathway. The results in mice suggested that Que can inhibit the release of inflammatory cytokine, block neutrophil recruitment, and decrease the albumin leakage in dose-dependent manners. At the same time, Que can increase the cAMP content of lung tissue, and Epac content, except PKA. The results in epithelial cell (MLE-12) suggested that Que also can inhibit the inflammatory mediators keratinocyte-derived chemokines release after LPS stimulation; Epac inhibitor ESI-09 functionally antagonizes the inhibitory effect of Que; meanwhile, PKA inhibitor H89 functionally enhances the inhibitory effect of Que. Overexpression of Epac1 in MLE-12 suggested that Epac1 enhance the effect of Que. All those results suggested that the protective effect of quercetin in ALI is involved in cAMP-Epac pathway.
槲皮素（Que）作为一种丰富的类黄酮元素，具有很强的抗氧化特性，并对脂多糖（LPS）诱导的急性肺损伤（ALI）具有保护作用，但具体机制尚不清楚，因此我们从体内和体外研究了 Que 的作用及其 cAMP-PKA/Epac 通路的相关机制。在小鼠中的结果表明，Que 可以抑制炎症细胞因子的释放，阻止中性粒细胞的募集，并以剂量依赖的方式减少白蛋白的渗漏。同时，Que 可以增加肺组织中的 cAMP 含量和 Epac 含量，但不增加 PKA。在肺上皮细胞（MLE-12）中的结果表明，Que 还可以抑制 LPS 刺激后炎症介质角质形成细胞衍生趋化因子的释放；Epac 抑制剂 ESI-09 可拮抗 Que 的抑制作用；同时，PKA 抑制剂 H89 可增强 Que 的抑制作用。在 MLE-12 中转染 Epac1 后，发现 Epac1 增强了 Que 的作用。这些结果表明，槲皮素在 ALI 中的保护作用涉及 cAMP-Epac 通路。
