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

被引:168
作者
Jiang, Wenjiao [1 ]
Luo, Fen [2 ]
Lu, Qianfeng [1 ]
Liu, Jingyan [2 ]
Li, Peijin [1 ]
Wang, Xiaofan [4 ]
Fu, Yeliu [3 ]
Hao, Kun [1 ]
Yan, Tianhua [1 ,2 ]
Ding, Xuansheng [1 ,5 ]
机构
[1] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
[2] China Pharmaceut Univ, Dept Physiol & Pharmacol, Nanjing 210009, Jiangsu, Peoples R China
[3] Zhejiang Univ, Sch Med, Affiliated Hosp 4, Yiwu 322000, Peoples R China
[4] China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China
[5] China Pharmaceut Univ, Dept Clin Pharm, Nanjing 210009, Jiangsu, Peoples R China
关键词
Trillin; Acute lung injury; Nrf2; HO-1; NF-kappa B; NF-KAPPA-B; SIGNALING PATHWAYS; MICROGLIAL CELLS; PLATYCODIN D; CROSS-TALK; MICE; NRF2; MACROPHAGES; INHIBITION; STRESS;
D O I
10.1016/j.cbi.2015.09.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:127 / 134
页数:8
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