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落新妇苷通过抑制丝裂原活化蛋白激酶(MAPK)信号通路和保护肺内皮糖萼来减轻脂多糖诱导的急性呼吸窘迫综合征。

Astilbin alleviates LPS-induced ARDS by suppressing MAPK signaling pathway and protecting pulmonary endothelial glycocalyx.

作者信息

Kong Guiqing, Huang Xiao, Wang Lipeng, Li Yan, Sun Ting, Han Shasha, Zhu Weiwei, Ma Mingming, Xu Haixiao, Li Jiankui, Zhang Xiaohua, Liu Xiangyong, Wang Xiaozhi

机构信息

Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China; Department of Biotechnology, Binzhou Medical University, Yantai 264003, Shandong Province, China.

Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China.

出版信息

Int Immunopharmacol. 2016 Jul;36:51-58. doi: 10.1016/j.intimp.2016.03.039. Epub 2016 Apr 22.

Abstract

Acute respiratory distress syndrome (ARDS) is a devastating disorder that is characterized by increased vascular endothelial permeability and inflammation. Unfortunately, no effective treatment beyond supportive care is available for ARDS. Astilbin, a flavonoid compound isolated from Rhizoma Smilacis Glabrae, has been used for anti-hepatic, anti-arthritic, and anti-renal injury treatments. This study examined the effects of Astilbin on pulmonary inflammatory activation and endothelial cell barrier dysfunction caused by Gram-negative bacterial endotoxin lipopolysaccharide (LPS). Endothelial cells from human umbilical veins or male Kunming mice were pretreated with Astilbin 24h before LPS stimulation. Results showed that Astilbin significantly attenuated the pulmonary histopathological changes and neutrophil infiltration 6h after the LPS challenge. Astilbin suppressed the activities of myeloperoxidase and malondialdehyde, as well as the expression of tumor necrosis factor-α and interleukin-6 in vivo and in vitro. As indices of pulmonary edema, lung wet-to-dry weight ratios, were markedly decreased by Astilbin pretreatment. Western blot analysis also showed that Astilbin inhibited LPS-induced activation of mitogen-activated protein kinase (MAPK) pathways in lung tissues. Furthermore, Astilbin significantly inhibited the activity of heparanase and reduced the production of heparan sulfate in the blood serum as determined by ELISA. These findings indicated that Astilbin can alleviate LPS-induced ARDS, which potentially contributed to the suppression of MAPK pathway activation and the degradation of endothelial glycocalyx.

摘要

急性呼吸窘迫综合征(ARDS)是一种破坏性疾病,其特征为血管内皮通透性增加和炎症反应。不幸的是,除了支持治疗外,尚无针对ARDS的有效治疗方法。蛇葡萄素是从土茯苓中分离出的一种黄酮类化合物,已被用于抗肝、抗关节炎和抗肾损伤治疗。本研究考察了蛇葡萄素对革兰氏阴性菌内毒素脂多糖(LPS)所致肺部炎症激活和内皮细胞屏障功能障碍的影响。人脐静脉内皮细胞或雄性昆明小鼠在LPS刺激前24小时用蛇葡萄素预处理。结果显示,LPS攻击6小时后,蛇葡萄素显著减轻了肺部组织病理学变化和中性粒细胞浸润。蛇葡萄素在体内和体外均抑制了髓过氧化物酶和丙二醛的活性,以及肿瘤坏死因子-α和白细胞介素-6的表达。作为肺水肿指标的肺湿重与干重之比,经蛇葡萄素预处理后显著降低。蛋白质印迹分析还表明,蛇葡萄素抑制LPS诱导的肺组织中丝裂原活化蛋白激酶(MAPK)通路的激活。此外,酶联免疫吸附测定结果显示,蛇葡萄素显著抑制乙酰肝素酶的活性,并降低血清中硫酸乙酰肝素的产生。这些发现表明,蛇葡萄素可减轻LPS诱导的ARDS,这可能是由于其抑制了MAPK通路的激活以及内皮糖萼的降解。

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