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3,4-二羟基苯乙酮通过抑制 ROS 介导的 MAPK 和 PI3K/AKT 信号通路下调 MMP-2 和 MMP-9 的活性来减轻脂多糖诱导的急性肺损伤中的炎症反应。

3, 4-dihydroxybenzalacetone attenuates lipopolysaccharide-induced inflammation in acute lung injury via down-regulation of MMP-2 and MMP-9 activities through suppressing ROS-mediated MAPK and PI3K/AKT signaling pathways.

机构信息

Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan.

Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.

出版信息

Int Immunopharmacol. 2017 Sep;50:77-86. doi: 10.1016/j.intimp.2017.06.014. Epub 2017 Jun 20.

DOI:10.1016/j.intimp.2017.06.014
PMID:28644965
Abstract

3, 4-Dihydroxybenzalacetone (DBL) is a constituent of Phellinus linteus. This study demonstrated the protective effect of DBL on lipopolysaccharide (LPS)-induced acute lung injuries in mice. Pretreatment with DBL significantly improved LPS-induced histological alterations in lung tissues. In addition, DBL markedly reduced the total cell number, the leukocytes, the protein concentrations, and decreased the release of nitrite, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and the activities of matrix metalloproteinase (MMP)-2 and -9 in the bronchoalveolar lavage fluid. DBL also inhibited the W/D ratio and myeloperoxidase activity in the lung tissues. Western blot analysis indicated DBL efficiently blocked the protein expressions of inducible nitric oxide synthase, cyclooxygenase-2, MMP-2, MMP-9, and the phosphorylation of mitogen-activated protein kinase (MAPK), phosphoinositide-3-kinase (PI3K), AKT, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Moreover, DBL enhanced the expression of anti-oxidant proteins, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Based on our results, DBL might be a potential target for attenuating tissue oxidative injuries and nonspecific pulmonary inflammation.

摘要

3,4-二羟基苯乙酮(DBL)是香菇中的一种成分。本研究表明 DBL 对脂多糖(LPS)诱导的小鼠急性肺损伤具有保护作用。DBL 预处理可显著改善 LPS 诱导的肺组织组织学改变。此外,DBL 可显著减少总细胞数、白细胞数、蛋白浓度,并降低支气管肺泡灌洗液中亚硝酸盐、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6 和基质金属蛋白酶(MMP)-2 和 -9 的活性。DBL 还抑制肺组织中的 W/D 比值和髓过氧化物酶活性。Western blot 分析表明,DBL 能有效阻断诱导型一氧化氮合酶、环氧化酶-2、MMP-2、MMP-9 的蛋白表达,以及丝裂原活化蛋白激酶(MAPK)、磷酸肌醇 3-激酶(PI3K)、AKT、Toll 样受体 4(TLR4)和核因子(NF)-κB 的磷酸化。此外,DBL 增强了抗氧化蛋白如超氧化物歧化酶(SOD)、过氧化氢酶和谷胱甘肽过氧化物酶(GPx)的表达。基于我们的研究结果,DBL 可能是减轻组织氧化损伤和非特异性肺炎症的潜在靶点。

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