p38MAPK信号通路在内毒素性休克诱发急性肺损伤大鼠肺组织HO-1表达上调中的作用  

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

作　　者：武丽娜[1] 余剑波[2] 刘大全[3] 宫丽荣[2] 王曼[2] 曹新顺[2] 闫雨苗[2] 

机构地区：[1]天津医科大学研究生院,300070 [2]天津市南开医院麻醉科 [3]天津市中西医结合急腹症研究所

出　　处：《中华麻醉学杂志》2012年第6期727-731,共5页Chinese Journal of Anesthesiology

基　　金：天津市卫生局科技基金（2010kz39）

摘　　要：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0．5ml；LS和LSS组股静脉注：射LPS10mg／kg（溶于0．5ml生理盐水）；2h内MAP下降至基础值的75％时，C组和LS组股静脉输注10％二甲基亚砜0．1ml；LSS组和sB组股静脉输注SB2035805μmol／kg（溶于0．1ml10％二甲基亚砜），输注速率0．01m／／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．1mRNA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，LS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-1mRNA及其蛋白和p-p38MAPK礓白的表达上调（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．1mRNA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。Objective To evaluate the role of p38MAPK signaling pathway in the up-regulation of heme oxygenase-1 （HO-1） expression in the lung tissue in rats with acute lung injury （ALI） induced by endotoxic shock.Methods Forty-eight male SD rats, aged 8 weeks, weighing 180-200 g, were randomly divided into 4 groups （ n = 12 each） ： control group （ group C ） ; endotoxic shock group （ group LS ） ; endotoxic shock ＋ SB203580 （ a specific p38MAPK inhibitor） group （ group LSS） and SB203580 group （ group SB ）. Normal saline 0.5 ml was injected via the femoral vein in groups C and SB, while LPS 10 mg/kg （in 0.5 ml normal saline） was injected via the femoral vein in groups LS and ISS. When MAP was decreased to 75% of baseline value, 10% dimethyl sulfoxide （DMSO） 0.1 ml was infused via the femoral vein in groups C and LS, while SB203580 5 /~mol/kg （in 10% DMSO 0.1 ml） was infused via the femoral vein at a rate of0.O1 ml/min in groups LSS and SB. Arterial blood samples were obtained at 6 h after LPS or normal saline was given for blood gas analysis and oxygenation index （PaO2/FiO2 ） was calculated. Then the rats were sacrificed and the lungs were removed for microscopic examination. The pathological changes of the lung were scored. The lung water content was calculated. The MDA content, SOD activity, and expression of HO-1 mRNA and protein, p38MAPK protein and phospharylated p38MAPK （p-p38MAPK） protein were determined. Results Compared with group C, the oxygenation index and SOD activity were significantly decreased, the pathological score, lung water content and MDA content were signif- icantly increased, and the expression of HO-1 mRNA and protein and p-p38MAPK protein was significantly up-regulated （ P 〈 0.05）, while no significant change was found in p38MAPK protein expression in groups LS and LSS, and no significant change was found in the indexes mentioned above in group SB （ P 〉 0.05 ）. Compared with group LS, the oxygenation index and SOD activity were signif

关 键 词：P38丝裂原活化蛋白激酶类 血红素加氧酶-1 肺 休克 脓毒性 呼吸窘迫综合征 成人 

分 类 号：R459.7[医药卫生—急诊医学]