The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state

The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state
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DOI:
10.1016/j.cbi.2015.09.010
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发表时间:
2016-01-05
影响因子:
5.1
通讯作者:
Ding, Xuansheng
Ding, Xuansheng
中科院分区:
医学2区
文献类型:
--
作者:
Jiang, Wenjiao;Luo, Fen;Ding, Xuansheng

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据报道,炎症反应和氧化应激参与了急性肺损伤(ALI)的发病机制。因此,抗炎治疗被认为是治疗ALI的一种可能有效的策略。本研究旨在评估延龄草苷(Tr)对脂多糖(LPS)诱导的小鼠ALI的抗炎功效,并探讨其潜在机制。BALB/c小鼠在气管内滴注脂多糖(LPS)刺激前1小时腹腔注射延龄草苷(50、100 mg/kg)。50、100 mg/kg剂量的延龄草苷预处理显著改善了肺湿干重(W/D)比、髓过氧化物酶(MPO)活性和肺组织病理学状况。此外,延龄草苷的保护作用可能归因于支气管肺泡灌洗液(BALF)中中性粒细胞浸润、丙二醛(MDA)、炎症细胞因子的下调以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH - Px)的上调。同时,我们的研究揭示了(核因子E2相关因子2)Nrf2/血红素加氧酶(HO)-1/核因子-κB(NF - κB)通路与延龄草苷的有益作用之间存在一些相关性,表现为肺组织中HO - 1和Nrf2蛋白表达显著上调以及p - NF - κB和NF - κB抑制蛋白(IκB)磷酸化水平下调。综上所述,我们的结果表明延龄草苷通过激活Nrf2、HO - 1和NF - κB通路调节相关炎症事件,对LPS诱导的ALI表现出保护作用。本研究表明延龄草苷可能是治疗ALI的一种潜在有效候选药物。(C)2015爱思唯尔爱尔兰有限公司。保留所有权利。
Inflammation response and oxidative stress have been reported to be involved in the pathogenesis of acute lung injury (ALI). Accordingly, anti-inflammatory treatment is proposed to be a possible efficient therapeutic strategy for ALI. The purpose of our present study was to evaluate the anti-inflammatory efficacy of trillin (Tr) on ALI induced by lipopolysaccharide (LPS) in mice and explore the underlying mechanism. BALB/c mice received Tr (50, 100 mg/kg) intraperitoneally 1 h prior to the intratracheal instillation of lipopolysaccharide (LPS) challenge. Pretreatment with Tr at the dose of 50, 100 mg/kg markedly ameliorated lung wet-to-dry weight (W/D) ratio, myeloperoxidase (MPO) activity and pulmonary histopathological conditions. In addition, the protective efficacy of Tr might be attributed to the down-regulations of neutrophil infiltration, malondialdehyde (MDA), inflammatory cytokines and the up-regulations of super-oxide dismutase (SOD), catalase(CAT), glutathione(GSH), Glutathione Peroxidase(GSH-Px) in bronchoalveolar lavage fluid (BALF). Meanwhile, our study revealed some correlations between (NF-E2-related factor 2) Nrf2/heme oxygenase (HO)-1/nuclear factor-kappa B (NF-kappa B) pathways and the beneficial effect of Tr, as evidenced by the significant up-regulations of HO-1 and Nrf2 protein expressions as well as the down-regulations of p-NF-kappa B and p-inhibitor of NF-kappa B (I kappa B) in lung tissues. Taken together, our results indicated that Tr exhibited protective effect on LPS-induced ALI by the regulations of related inflammatory events via the activations of Nrf2, HO-1 and NF-kappa B pathway. The current study indicated that Tr could be a potentially effective candidate medicine for the treatment of ALI. (C) 2015 Elsevier Ireland Ltd. All rights reserved.