Apigetrin treatment attenuates LPS- induced acute otitis media though suppressing inflammation and oxidative stress
Apigetrin treatment attenuates LPS- induced acute otitis media though suppressing inflammation and oxidative stress
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DOI：
10.1016/j.biopha.2018.07.022
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发表时间：
2019-01-01
影响因子：
7.5
通讯作者：
Xu, Li-Juan
中科院分区：
文献类型：
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作者：
Guo, Hao;Li, Ming;Xu, Li-Juan
儿童中耳炎的自然病程是急性且具有自限性。然而，约10 - 20%的儿童可能会经历复发性或持续性中耳炎。因此，迫切需要找到预防急性中耳炎的有效候选物。在我们的研究中，通过经鼓膜向小鼠中耳注射脂多糖（LPS）构建了小鼠急性中耳炎模型。芹菜素（APT）是一种从多种草药中分离出的黄酮类化合物，具有抗炎和抗氧化生物活性。然而，APT是否能减轻LPS诱导的动物模型中的急性中耳炎，人们知之甚少。苏木精 - 伊红（H&E）染色表明，APT治疗降低了LPS诱导的较高的黏膜厚度。APT还抑制了LPS引发的炎症反应，中性粒细胞和巨噬细胞的下调证明了这一点。此外，在接受APT治疗的急性中耳炎小鼠中，观察到炎症因子减少，包括白细胞介素 - 1β（IL - 1β）、肿瘤坏死因子α（TNF - α）、IL - 6和血管内皮生长因子（VEGF）。这一过程与抑制Toll样受体4（TLR4）/核因子κB（NF - κB）通路有关，通过蛋白质印迹分析对TLR4、MyD88、p - IKKα、p - IκBα和p - NF - κB的阻断证明了这一点。此外，APT通过促进抗氧化剂，包括超氧化物歧化酶（SOD）活性、血红素加氧酶 - 1（HO - 1）、NADP（H）醌氧化还原酶1（NQO - 1）和核因子红细胞2相关因子2（Nrf2）的表达，降低了LPS引起的活性氧（ROS）的产生。相反，APT下调了LPS处理小鼠中高水平的丙二醛（MDA）和类Kelch的ECH相关蛋白1（Keap1），这可能与NF - κB的失活有关。在体外，APT在LPS刺激的细胞中表现出抗炎和抗氧化作用，且细胞毒性很小。综上所述，上述数据表明APT可通过抑制炎症和氧化应激来改善急性中耳炎。
The natural course of otitis media in children is acute and self-limiting. Nevertheless, about 10-20% children could experience recurrent or persistent otitis media. Thus, finding effective candidate to prevent acute otitis media is urgently required. In our study, mouse acute otitis media model was constructed by lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane. Apigetrin (APT) is a flavonoid isolated from various herbal medicines, possessing anti-inflammatory and anti-oxidative bioactivities. However, if APT could attenuate acute otitis media in LPS-induced animal models, little is to be known. Hematoxylin and eosin (II & E) staining suggested that APT treatment reduced LPS-induced higher mucosa thickness. LPS-triggered inflammatory response was also inhibited by APT, as evidenced by the down-regulated neutrophils and macrophages. Additionally, the reduced inflammatory factors, including interleukin-1 beta (IL-l beta), tumor necrosis factor a (TNF-alpha), IL-6 and vascular endothelial growth factor (VEGF) were observed in APT-treated mice with acute otitis media. The process was associated with the inhibition of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-kappa B) pathway, which was proved by the blockage of TLR4, MyD88, p-IKK alpha, p-I kappa Ba, and p-NF-kappa B using western blot analysis. Moreover, the production of reactive oxygen species (ROS) caused by LPS was also reduced by APT through promoting anti-oxidants, involving superoxide dismutase (SOD) activity, heme oxygenase-1 (HO-1), NADP(H) quinone oxidoreductase 1 (NQO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions. In contrast, high levels of MDA and kelch-like ECH-associated protein 1 (Keap 1) in LPS-treated mice were down-regulated by APT, which might be associated with the inactivation of NF-kappa B. In vitro, APT exhibited anti-inflammatory and anti-oxidant effects with little cytotoxicity in LPS-stimulated cells. Together, the data above indicated that APT could ameliorate acute otitis media through inhibiting inflammation and oxidative stress.