Sivelestat sodium attenuates acute lung injury by inhibiting JNK/NF-κB and activating Nrf2/HO-1 signaling pathways.
Sivelestat sodium attenuates acute lung injury by inhibiting JNK/NF-κB and activating Nrf2/HO-1 signaling pathways.
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西维来司他钠通过抑制 JNK/NF-κB 和激活 Nrf2/HO-1 信号通路减轻急性肺损伤
DOI：
10.17305/bb.2022.8549
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发表时间：
2023-05-01
期刊：
影响因子：
--
通讯作者：
Lv, Chuanzhu
中科院分区：
文献类型：
--
作者：
Zhang, Hong;Zeng, Jun;Li, Jiankang;Gong, Huankai;Chen, Meiling;Li, Quan;Liu, Shengxing;Luo, Shanjun;Dong, Huanxiang;Xu, Yingke;Duan, Huanling;Huang, Ling;Lv, Chuanzhu
西维来司他钠（SIV）是一种中性粒细胞弹性蛋白酶抑制剂，主要用于急性呼吸窘迫综合征（ARDS）或急性肺损伤（ALI）的临床治疗。然而，关于SIV治疗ALI效果的研究有限。因此，本研究探讨了SIV对ALI保护作用的潜在分子机制。用肿瘤坏死因子α（TNF -α）刺激人肺微血管内皮细胞（HPMECs），对雄性Sprague - Dawley大鼠气管内注射肺炎克雷伯菌（KP），并用SIV、ML385和茴香霉素（ANI）进行处理，分别在体外和体内模拟ALI的发病过程。在体外和体内评估炎症细胞因子水平和氧化应激指标。分析肺组织的湿/干（W/D）比、组织病理学变化、支气管肺泡灌洗液（BALF）中炎症细胞水平以及大鼠的存活率。通过蛋白质印迹和免疫荧光分析来分析HPMECs和肺组织中JNK/NF -κB（p65）和Nrf2/HO - 1的水平。给予SIV可降低肺组织中炎症因子水平、细胞内活性氧（ROS）产生以及丙二醛（MDA）水平，并提高超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH - Px）的水平。同时，SIV减轻了病理损伤，降低了肺组织的W/D比以及炎症细胞浸润。此外，SIV还抑制了JNK/NF -κB信号通路的激活，促进了Nrf2的核转位，并上调了血红素加氧酶1（HO - 1）的表达。然而，ANI或ML385显著逆转了这些变化。SIV有效地减轻了炎症反应和氧化应激。其潜在分子机制与JNK/NF -κB激活以及Nrf2/HO - 1信号通路抑制有关。这进一步加深了对SIV抗ALI保护作用的理解。
Sivelestat sodium (SIV), a neutrophil elastase inhibitor, is mainly used for the clinical treatment of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). However, studies investigating the effects of SIV treatment of ALI are limited. Therefore, this study investigated the potential molecular mechanism of the protective effects of SIV against ALI. Human pulmonary microvascular endothelial cells (HPMECs) were stimulated with tumor necrosis factor α (TNF-α), and male Sprague–Dawley rats were intratracheally injected with Klebsiella pneumoniae (KP) and treated with SIV, ML385, and anisomycin (ANI) to mimic the pathogenetic process of ALI in vitro and in vivo, respectively. The levels of inflammatory cytokines and indicators of oxidative stress were assessed in vitro and in vivo. The wet/dry (W/D) ratio of lung tissues, histopathological changes, inflammatory cells levels in bronchoalveolar lavage fluid (BALF), and survival rates of rats were analyzed. The JNK/NF-κB (p65) and Nrf2/HO-1 levels in the HPMECs and lung tissues were analyzed by western blot and immunofluorescence analyses. Administration of SIV reduced the inflammatory factors levels, intracellular reactive oxygen species (ROS) production, and malondialdehyde (MDA) levels and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissues. Meanwhile, SIV alleviated pathological injuries, decreased the W/D ratio, and inflammatory cell infiltration in lung tissue. In addition, SIV also inhibited the activation of JNK/NF-κB signaling pathway, promoted nuclear translocation of Nrf2, and upregulated the expression of heme oxygenase 1 (HO-1). However, ANI or ML385 significantly reversed these changes. SIV effectively attenuated the inflammatory response and oxidative stress. Its potential molecular mechanism was related to the JNK/NF-κB activation and Nrf2/HO-1 signaling pathway inhibition. This further deepened the understanding of the protective effects of SIV against ALI.
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影响因子：
5.1
作者：
Jiang, Wenjiao;Luo, Fen;Ding, Xuansheng
通讯作者：
Ding, Xuansheng
影响因子：
12.7
作者：
Kolilekas, Lykourgos;Loverdos, Konstantinos;Gaga, Mina
通讯作者：
Gaga, Mina
影响因子：
7.2
作者：
Huang, Jia-Luo;Fan, Run-Zhu;Tang, Gui-Hua
通讯作者：
Tang, Gui-Hua
DOI：
10.3390/foods11030364
发表时间：
2022-01-27
期刊：
Foods (Basel, Switzerland)
影响因子：
--
作者：
Kim EA;Kang N;Kim J;Yang HW;Ahn G;Heo SJ
通讯作者：
Heo SJ
影响因子：
2.5
作者：
Luo S;Gan L;Liu S;Zhong L;Chen M;Zhang H;Li J;Huang L;Lv C
通讯作者：
Lv C