摘要
目的评价阿司匹林诱生型脂氧素A4(ATL)对脂多糖(LPS)诱导小鼠急性肺损伤的影响。方法雄性SPF级BALB/C小鼠30只,体重25~30g,10~12周龄,采用随机数字表法,将其分为3组(n=10):对照组(Ns组)气管内滴定生理盐水(LPS溶媒)1.5ml/kg,1h后尾静脉注射50%无水乙醇(ATL溶媒)0.1ml;LPS组气管内滴定LPS3mg/kg,1h后尾静脉注射50%无水乙醇0.1ml;ATL组气管内滴定LPS3mg/kg,1h后尾静脉注射ATL0.2mg/kg。气管内滴定药物后24h处死,采集支气管肺泡灌洗液(BALF),计数总细胞数、多形核粒细胞比例、单个核细胞比例及其总蛋白、TNF-α、IL-6、单核细胞趋化蛋白-1(MCP-1)、IL-10的浓度;取肺组织,测定髓过氧化物酶(MPO)活性、p38丝裂原活化蛋白激酶(p38MAPK)、c—Jun氨基末端激酶(JNK)、细胞外调节蛋白激酶(ERK1/2)的磷酸化水平,并观察肺组织病理学结果,行肺损伤评分。结果与Ns组比较,LPS组和ArrL组肺损伤评分、BALF中总细胞数、多形核粒细胞比例、TNF-α、IL-6、MCP-1浓度升高,单个核粒细胞比例降低,LPS组BALF中IL-IO浓度降低,总蛋白浓度、肺组织MPO活性、p38MAPK、JNK、ERK1/2的磷酸化水平升高(P〈0.05),ATL组BALF中总蛋白、IL-10浓度、肺组织MPO活性、p38MAPK、JNK、ERK1/2的磷酸化水平差异无统计学意义(P〉0.05);与LPS组比较,ATL组肺损伤评分、BALF中总细胞数、多形核粒细胞比例和总蛋白、TNF—α、IL-6、MCP-1浓度降低,单个核粒细胞比例和IL-10浓度升高,肺组织MPO活性、p38MAPK和JNK的磷酸化水平降低(P〈0.05),ERK1/2的磷酸化水平差异无统计学意义(P〉0.05)。结论ATL可减轻LPS诱导的小鼠急性肺损伤,其机制与抑制p38MAPK和JNK信号通路激活有关。
Objective To evaluate the effects of aspirin-triggered lipoxin A4 (ATL) on lipopolysaccharide (LPS)-induced acute lung injury in mice. Methods Thirty male SPF BALB/C mice, aged 10-12 weeks, weighing 25-30 g, were randomly assigned into 3 groups ( n = 10 each) : normal saline group (group NS), LPS group and ATL groups. ATL 0.1 ml was injected via the tail vein 1 h after intra-tracheal instillation of 3 mg/kg LPS in LPS group. In ATL group, ATL 0.2 mg/kg was injected via the tail vein 1 h after intra-tracheal instillation of 3 mg/kg LPS. At 24 h after instillation, the mice were sacrificed. Bronchoalveolar lavage fluid was collected for determination of the total cell count, proportion of the polymorphonuclear leukocytes, proportion of the mononuclear leukocytes, and concentrations of the total protein, TNF-α, IL-6, monocyte chemoattractant protein- 1 ( MCP- 1 ) and IL-10. Lungs were removed for determination of myeloperoxidase (MPO) activity, phosphorylation of p38 mitogen- activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2) in lung tissues and for microscopic examination. The pathological changes of lungs were scored. Results Compared with NS group, the lung injury scores, total cell counts, proportion of polymorphonuclear leukocytes, and concentrations of TNF-α, IL-6 and MCP-1 were significantly increased, and the proportion of mononuclear leukocytes was decreased in LPS and ATL groups, and IL-10 concentrations were decreased, and the concentrations of the total protein, MPO activity, and phosphorylation of p38 MAPK, JNK and ERK1/2 were significantly increased in group LPS ( P 〈 0.05), and no significant change in the concentrations of the total protein, MPO activity, phosphorylation of p38 MAPK, JNK and ERK1/2 was found in group ATL ( P 〉 0.05) . Compared with LPS group, the lung injury scores, total cell counts, proportion of polymorphonuclear leukocytes and the concentrations of the total
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2013年第5期595-598,共4页
Chinese Journal of Anesthesiology
基金
国家自然科学基金(30930089)
卫生部临床重点学科项目(2010-47)