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Role of p38MAPK signaling pathway in up-regulation of heme oxygenase-1 expression in lung tissues in rats with acute lung injury induced by endotoxic shock
Author(s): WU Li-na, YU Jian-bo, LIU Da-quan, GONG Li-rong, WANG Man, CAO Xin-shun, YAN Yu-miao
Pages: 727-
731
Year: 2012
Issue:
6
Journal: Chinese Journal of Anesthesiology
Keyword: p38 Mitogen-activated protein kinases; Hemne oxygenase-1; Lung; Shock; septic; Respiratory distress syndrome; adult;
Abstract: 目的 评价p38丝裂原活化蛋白激酶(p38MAPK)信号通路在内毒素性休克诱发急性肺损伤大鼠肺组织血红素加氧酶-1(HO-1)表达上调中的作用.方法 雄性SD大鼠48只,8周龄,体重180~ 200g,采用随机数字表法,将其随机分为4组(n=12):对照组(C组)、内毒素性休克组(LS组)、内毒素性休克+ p38MAPK特异性抑制剂SB203580组(LSS组)和SB203580组(SB组).C组和SB组股静脉注射生理盐水0.5 ml;LS和LSS组股静脉注射LPS 10 mg/kg(溶于0.5ml生理盐水);2h内MAP下降至基础值的75%时,C组和IS组股静脉输注10%二甲基亚砜0.1ml;LSS组和SB组股静脉输注SB203580 5 μmol/kg(溶于0.1 ml 10%二甲基亚砜),输注速率0.01 ml/min.给予LPS或生理盐水后6h时采集动脉血样,进行血气分析,计算氧合指数(PaO2/FiO2);然后处死大鼠取肺组织,光镜下观察病理学结果,并进行病理学损伤评分,计算肺含水率,测定SOD活性、MDA含量、HO-1 mRNA及其蛋白、p38MAPK蛋白和磷酸化p38MAPK(p-p38MAPK)蛋白的表达.结果 与C组比较,IS组和LSS组氧合指数和SOD活性降低,病理学损伤评分、肺含水率和MDA含量升高,肺组织HO-1 mRNA及其蛋白和p-p38MAPK蛋白的表达上调(P<0.05),p38MAPK蛋白表达差异无统计学意义,SB组各指标差异无统计学意义(P>0.05);与LS组比较,LSS组氧合指数和SOD活性升高,病理学损伤评分、肺含水率和MDA含量降低,肺组织HO-1 mRNA及其蛋白表达上调,p-p38MAPK蛋白表达下调(P<0.05),p38MAPK蛋白表达差异无统计学意义(P>0.05).结论 抑制p38MAPK信号通路可导致内毒素性休克诱发急性肺损伤大鼠肺组织HO-1表达上调.
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