Cai Xueding, Chen Yanfan, Xie Xiaona, Yao Dan, Ding Cheng, Chen Mayun
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
Pulmonary Division, Zhejiang University of Traditional Chinese Medicine Affiliated with Wenzhou Hospital Wenzhou 325000, Zhejiang, P. R. China.
Am J Transl Res. 2019 Mar 15;11(3):1884-1894. eCollection 2019.
Endotoxin-induced acute inflammatory diseases such as sepsis, mediated by excessive production of various pro-inflammatory cytokines remain the leading cause of mortality in critically ill patients. Lipopolysaccharide (LPS), the characteristic endotoxin found in the outer membrane of Gram-negative bacteria, can induce the innate immunity system and through Mitogen activated protein kinase (MAPK) and Nuclear Factor-κB (NF-κB), increase the production of inflammatory mediators. Astaxanthin (ASX), a xanthophyll carotenoid, exerts beneficial effects against oxidation, inflammation, and cancer. But poor evidence has been reported that whether it has protective effects on LPS-induced injury. This study aims to investigate the effects of ASX on LPS-induced sepsis and acute lung injury and to demonstrate its mechanisms.
Mouse prime macrophage (MPM) challenged with LPS were used for in vitro pharmacological activity and mechanistic studies. Inflammatory facors (tumor necrosis factor-alpha and interleukin-6 levels) in MPM were determined. The mouse models of LPS-induced sepsis and acute lung injury administrated with or without the compound were used for in vivo studies.
Pre-treatment of MPM with ASX inhibited MAPK/NF-κB signaling pathway, and attenuated LPS-increased inflammatory factors in vitro. In animal models of LPS-induced sepsis and acute lung injury, administration of ASX significantly improved survival and protected lung injury. Subsequently, ASX was shown to suppress LPS-induced inflammatory factors increase, MAPK phosphorylation, and NF-κB activation .
ASX exerts impressively protective effects on LPS-induced injury and . Taken together, it might be used as a potential candidate for clinical sepsis.
内毒素诱导的急性炎症性疾病，如脓毒症，由各种促炎细胞因子的过度产生介导，仍然是重症患者死亡的主要原因。脂多糖（LPS）是革兰氏阴性菌外膜中发现的特征性内毒素，可诱导先天免疫系统，并通过丝裂原活化蛋白激酶（MAPK）和核因子-κB（NF-κB）增加炎症介质的产生。虾青素（ASX）是一种叶黄素类胡萝卜素，对氧化、炎症和癌症具有有益作用。但关于它是否对LPS诱导的损伤具有保护作用的证据不足。本研究旨在探讨ASX对LPS诱导的脓毒症和急性肺损伤的影响，并阐明其机制。
用LPS刺激的小鼠原代巨噬细胞（MPM）进行体外药理活性和机制研究。测定MPM中的炎症因子（肿瘤坏死因子-α和白细胞介素-6水平）。使用给予或未给予该化合物的LPS诱导的脓毒症和急性肺损伤小鼠模型进行体内研究。
ASX预处理MPM可抑制MAPK/NF-κB信号通路，并在体外减弱LPS增加的炎症因子。在LPS诱导的脓毒症和急性肺损伤动物模型中，给予ASX可显著提高生存率并保护肺损伤。随后，ASX被证明可抑制LPS诱导的炎症因子增加、MAPK磷酸化和NF-κB激活。
ASX对LPS诱导的损伤具有显著的保护作用。综上所述，它可能作为临床脓毒症的潜在候选药物。
