MaR1治疗脂多糖诱导的急性肺损伤小鼠的效果和机制  

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

作　　者：王强[1] 林飞[1] 胡召锟 林锦源 黄冰[1] 潘灵辉[1] WANG Qiang;LIN Fei;HU Zhao—kun;LIN Jin-yuan;HUANG Bing;PAN Ling-hui(Department of Anesthesiology,Affiliated Tumor Hospital,Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]广西医科大学附属肿瘤医院麻醉科,广西南宁530021

出　　处：《广东医学》2021年第8期909-913,共5页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(81460016,81970078)。

摘　　要：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。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).Conclusion The 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.

关 键 词：脂多糖 急性肺损伤 MaR1 核因子-E2相关因子2 

分 类 号：R452[医药卫生—治疗学] R614[医药卫生—临床医学]