Department of ICU, Shanghai Xuhui District Central Hospital, Shanghai, China.
Department of Galactophore, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong Province, China.
J Biol Regul Homeost Agents. 2020 May-Jun;34(3):807-814. doi: 10.23812/20-108-A-20.
The aim of the study was to explore the effect of lipoxin A4 (LXA4) on lung injury in sepsis rats through the p38/mitogen-activated protein kinase (MAPK) signaling pathway. Sprague-Dawley rats were used for the study. The rat model of sepsis-induced acute lung injury was established via cecal ligation (Sepsis group, n=20). LXA4 (0.1 mg/kg) was injected at 6 h after modeling (Treatment group, n=20), and a The Control group (n=20) was also set up. The 7-day survival rate was 100% in The Control group, and LXA4 raised the survival rate of rats in the Sepsis group from 40% to 60% (P<0.01). Alveolar fluid clearance (AFC) significantly declined and the wet/dry weight (W/D) ratio of lung tissues rose remarkably in the Sepsis group compared with those in the Control group, while LXA4 restored AFC and reduced the W/D ratio of lung tissues (P<0.05), suggesting that LXA4 treatment reduces lung fluids and partially enhances AFC, thus lowering the W/D ratio of lung. The total cell count, polymorphonuclear neutrophils (PMN) percentage and concentration of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were obviously increased in the Sepsis group compared with those in the Control group, while they were markedly decreased in the Treatment group (P<0.05). The activity of myeloperoxidase (MPO) in lung tissue homogenate was evidently higher in the Sepsis group than that in The Control group, while it was notably lower in the Treatment group than that in the Sepsis group after LXA4 treatment (P<0.05). Moreover, it was observed microscopically that the morphology of lung tissues was intact in the Control group. Finally, the results of Western blotting manifested that the p-p38/ MAPK protein expression was remarkably increased in the Sepsis group, indicating the activation of the p38/MAPK pathway, while it was remarkably decreased in the Treatment group, indicating the inhibited activity of the pathway (P<0.05). LXA4 has an anti-inflammatory effect on sepsis rats with lung injury, and such effect is related to the p38/MAPK signaling pathway.
本研究旨在通过 p38/丝裂原活化蛋白激酶（MAPK）信号通路探讨脂氧素 A4（LXA4）对脓毒症大鼠肺损伤的影响。采用 Sprague-Dawley 大鼠进行研究。通过盲肠结扎（Sepsis 组，n=20）建立脓毒症诱导的急性肺损伤大鼠模型。造模后 6 h 注射 LXA4（0.1 mg/kg）（治疗组，n=20），并设立对照组（n=20）。对照组大鼠 7 天存活率为 100%，LXA4 将 Sepsis 组大鼠的存活率从 40%提高至 60%（P<0.01）。与对照组相比，Sepsis 组肺泡液清除率（AFC）显著下降，肺组织湿/干重（W/D）比值明显升高，而 LXA4 则恢复了 AFC，并降低了肺组织的 W/D 比值（P<0.05），提示 LXA4 治疗可减少肺液并部分增强 AFC，从而降低肺 W/D 比值。Sepsis 组支气管肺泡灌洗液（BALF）中的总细胞计数、多形核粒细胞（PMN）百分比以及肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-6 浓度明显高于对照组，而治疗组明显低于 Sepsis 组（P<0.05）。肺组织匀浆髓过氧化物酶（MPO）活性在 Sepsis 组明显高于对照组，而经 LXA4 治疗后治疗组明显低于 Sepsis 组（P<0.05）。此外，显微镜下观察到对照组肺组织形态完整。最后，Western blot 结果显示，Sepsis 组 p-p38/MAPK 蛋白表达明显增加，表明 p38/MAPK 通路被激活，而治疗组则明显减少，表明通路活性受到抑制（P<0.05）。LXA4 对脓毒症大鼠肺损伤具有抗炎作用，这种作用与 p38/MAPK 信号通路有关。
