aR1治疗脂多糖诱导的急性肺损伤小鼠的效果和机制

目的 探讨Maresin-1（MaR1）治疗脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠的效果和机制。方法将雄性SPF级BALB/c小鼠45只随机分为3组。对照组经口气管插管滴入3 mg/kg生理盐水。LPS组经口气管插管滴入3 mg/kg LPS。MaR1组经口气管插管滴入3 mg/kg LPS，1 h后尾静脉注射1 ng/只MaR1。对比分析3组小鼠肺组织损伤评分、免疫印迹分析小鼠肺组织MAPKs、核因子-κB(NF-κB)蛋白表达，以及氧化应激标记分析3组小鼠肺组织核因子-E2相关因子2（Nrf-2）表达和抗氧化酶的情况。结果与LPS组比较，MaR1组能改善LPS诱导的ALI小鼠肺组织损伤评分（P=0.000）；MaR1组能显著抑制LPS诱导的ALI小鼠MAPKs和p65NF-κB的磷酸化，两组间差异均有统计学意义（P＜0.05）；MaR1组通过上调抗氧化酶增加Nrf-2的核转运，两组间差异均有统计学意义（P＜0.05）；MaR1组抑制了LPS诱导的ALI模型肺组织中活性氧介导的氧化应激反应，两组间差异均有统计学意义（P＜0.05）。结论MaR1治疗小鼠ALI机制可能是通过抑制MAPK和NF-κB的磷酸化，同时活化多种抗氧化酶保护肺组织有关。

Effect and mechanism of MaR1 on acute lung injury-induced by lipopolysaccharide in mice

Objective To investigate the effect and mechanism of maresin-1 (MaR1) on lipopolysaccharide-induced acute lung injury (ALI) in mice. Methods Forty-five male SPF BALB/c mice were randomly divided into 3 groups, control group (3 mg/kg normal saline was injected via endotracheal intubation), LPS group (3 mg/kg LPS via endotracheal intubation), and MaR1 group (3 mg/kg LPS via endotracheal intubation via endotracheal intubation). The expression of MAPKs, NF-κB, nuclear factor E2-related factor 2 (nrf-2) and antioxidant enzymes in the lung tissues of mice were compared. Results Compared with LPS group, MaR1 group significantly improved lung tissue injury score of ALI mice induced by LPS (P=0.000). The phosphorylation of MAPKs and p65 NF-κB in ALI mice induced by LPS was significantly inhibited in the MaR1 group (P<0.05). The nuclear transport of Nrf-2 was significantly increased by upregulation of antioxidant enzymes in the MaR1 group (P<0.05). The MaR1 group significantly inhibited the oxidative stress response mediated by reactive oxygen species in the lung tissue of LPS-induced ALI model (P<0.05). ConclusionThe mechanism of MaR1 in the treatment of ALI in mice may be related to the protection of lung tissue by inhibiting the phosphorylation of MAPK and NF-κB, and activating various antioxidant enzymes