Epigallocatechin-3-gallate ameliorates lipopolysaccharide-induced acute lung injury by suppression of TLR4/NF-κB signaling activation

Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. The activation of inflammation is well-recognized as a vital factor in the pathogenesis of lipopolysaccharide (LPS)-induced ALI. Therefore, suppression of the inflammatory response could be an ideal strategy to prevent ALI. Epigallocatechin-3-gallate (EGCG), mainly from green tea, has been shown to have an anti-inflammatory effect. The aim of the study was to explore whether EGCG alleviates inflammation in sepsis-related ALI. Male BALB/C mice were treated with EGCG (10 mg/kg) intraperitoneally (ip) 1 h before LPS injection (10 mg/kg, ip). The results showed that EGCG attenuated LPS-induced ALI as it decreased the changes in blood gases and reduced the histological lesions, wet-to-dry weight ratios, and myeloperoxidase (MPO) activity. In addition, EGCG significantly decreased the expression of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the lung, serum, and bronchoalveolar lavage fluid, and alleviated the expression of TLR-4, MyD88, TRIF, and p-p65 in the lung tissue. In addition, it increased the expression of IκB-α and had no influence on the expression of p65. Collectively, these results demonstrated the protective effects of EGCG against LPS-induced ALI in mice through its anti-inflammatory effect that may be attributed to the suppression of the activation of TLR 4-dependent NF-κB signaling pathways.

急性肺损伤（Acute lung injury, ALI）是一种病死率较高的严重临床综合征。炎症激活被公认为脂多糖（lipopolysaccharide, LPS）诱导型ALI发病机制中的关键致病因素。因此，抑制炎症反应可作为预防ALI的理想策略。表没食子儿茶素没食子酸酯（Epigallocatechin-3-gallate, EGCG）主要提取自绿茶，已被证实具有抗炎活性。本研究旨在探讨EGCG是否能够缓解脓毒症相关ALI的炎症反应。实验中，雄性BALB/C小鼠在腹腔注射脂多糖（10 mg/kg）前1小时，经腹腔给予EGCG（10 mg/kg）。结果显示，EGCG可减轻脂多糖诱导的ALI：其可改善血气指标异常、减轻肺组织病理损伤、降低湿干重比值以及髓过氧化物酶（myeloperoxidase, MPO）活性。此外，EGCG可显著下调肺组织、血清及支气管肺泡灌洗液中促炎细胞因子肿瘤坏死因子（tumor necrosis factor, TNF）-α、白细胞介素（interleukin, IL）-1β与IL-6的表达水平，并抑制肺组织中Toll样受体4（Toll-like receptor 4, TLR-4）、MyD88、TRIF及p-p65的表达。同时，EGCG可上调IκB-α的表达，而对总p65的表达无明显影响。综上，本研究结果表明，EGCG可通过其抗炎作用对小鼠脂多糖诱导的ALI发挥保护作用，其机制可能与抑制TLR4依赖的NF-κB信号通路激活有关。