Fibroblast growth factor-2 alleviates the capillary leakage and inflammation in sepsis.
Fibroblast growth factor-2 alleviates the capillary leakage and inflammation in sepsis.
复制标题
成纤维细胞生长因子-2减轻脓毒症中的毛细血管渗漏和炎症
DOI：
10.1186/s10020-020-00221-y
复制
发表时间：
2020-11-13
期刊：
影响因子：
--
通讯作者：
Pan J
中科院分区：
文献类型：
--
作者：
Pan X;Xu S;Zhou Z;Wang F;Mao L;Li H;Wu C;Wang J;Huang Y;Li D;Wang C;Pan J
急性肺损伤（acute lung injury，ALI）是由多种致病因素特别是脓毒症引起的，可导致肺泡损伤、肺水肿和血管通透性增高，最终导致严重低氧血症。成纤维细胞生长因子-2（Fibroblast growth factor-2，FGF-2）是FGF家族的重要成员，与内皮细胞的迁移、增殖和损伤修复有关。在此，我们进行了这项研究，旨在评估FGF 2在脓毒症诱导的ALI中的治疗作用。将重组FGF 2腹腔注射至盲肠结扎穿孔（CLP）诱导的脓毒症小鼠，检测其肺组织炎症因子、血管通透性及肺损伤相关指标的蛋白水平和基因表达。体外培养人肺微血管内皮细胞（HPMEC）和小鼠腹腔巨噬细胞（PMs），分别用脂多糖（LPS）和FGF 2刺激，检测炎症指标和细胞通透性的变化。结果显示，FGF 2治疗减少了脓毒症小鼠的炎症反应，减弱了肺毛细血管渗漏，减轻了肺损伤并提高了存活率。FGF 2通过AKT/P38/NF-κB信号通路抑制LPS诱导的内皮损伤和巨噬细胞炎症。这些发现表明FGF 2通过改善毛细血管渗漏和炎症在ALI中的治疗作用。
Acute lung injury (ALI), which is induced by numerous pathogenic factors, especially sepsis, can generate alveolar damage, pulmonary edema and vascular hyper-permeability ultimately leading to severe hypoxemia. Fibroblast growth factor-2 (FGF2) is an important member of the FGF family associated with endothelial cell migration and proliferation, and injury repairment. Here, we conducted this study aiming to evaluate the therapeutic effect of FGF2 in sepsis-induced ALI. Recombinant FGF2 was abdominally injected into septic mice induced by cecal ligation and puncture (CLP), and then the inflammatory factors of lung tissue, vascular permeability and lung injury-related indicators based on protein levels and gene expression were detected. In vitro, human pulmonary microvascular endothelial cells (HPMEC) and mouse peritoneal macrophages (PMs) were challenged by lipopolysaccharides (LPS) with or without FGF2 administration in different groups, and then changes in inflammation indicators and cell permeability ability were tested. The results revealed that FGF2 treatment reduced inflammation response, attenuated pulmonary capillary leakage, alleviated lung injury and improved survival in septic mice. The endothelial injury and macrophages inflammation induced by LPS were inhibited by FGF2 administration via AKT/P38/NF-κB signaling pathways. These findings indicated a therapeutic role of FGF2 in ALI through ameliorating capillary leakage and inflammation.
登录
查看更多内容
影响因子：
17.1
作者：
London NR;Zhu W;Bozza FA;Smith MC;Greif DM;Sorensen LK;Chen L;Kaminoh Y;Chan AC;Passi SF;Day CW;Barnard DL;Zimmerman GA;Krasnow MA;Li DY
通讯作者：
Li DY
影响因子：
16.6
作者：
Giano, Michael C.;Ibrahim, Zuhaib;Medina, Scott H.;Sarhane, Karim A.;Christensen, Joani M.;Yamada, Yuji;Brandacher, Gerald;Schneider, Joel P.
通讯作者：
Schneider, Joel P.
影响因子：
38.9
作者：
Rhodes, Andrew;Evans, Laura E.;Dellinger, R. Phillip
通讯作者：
Dellinger, R. Phillip
影响因子：
3.8
作者：
Ciesla, DJ;Moore, EE;Sauaia, A
通讯作者：
Sauaia, A
影响因子：
81.5
作者：
Matthay, Michael A.;Zemans, Rachel L.;Calfee, Carolyn S.
通讯作者：
Calfee, Carolyn S.