地塞米松对内毒素性急性肺损伤大鼠肺组织MKP-1表达的影响  

Effect of dexamethasone on MKP-1 expression in lung tissues in rats with lipopolysaccharide-induced acute lung injury

作　　者：成勤[1] 陈龙 刘苏[2] 张茂银[2] 张稳稳[2] 刘功俭[2] 

机构地区：[1]江苏省海门市人民医院麻醉科,226100 [2]徐州医学院江苏省麻醉医学研究所江苏省麻醉学重点实验室徐州医学院附属医院麻醉科 [3]江苏省徐州市第六人民医院

出　　处：《中华麻醉学杂志》2012年第2期214-217,共4页Chinese Journal of Anesthesiology

基　　金：江苏省“六大人才高峰”资助项目（06-B-065）

摘　　要：目的评价地塞米松对内毒素性急性肺损伤大鼠肺组织丝裂原活化蛋白激酶磷酸酶-1（MKP-1）表达的影响。方法成年雄性SD大鼠54只，体重180—230g，采用随机数字表法，将其随机分为3组：对照组（c组，n=6）、急性肺损伤组（ALI组，n=24）和地塞米松组（D组，n=24）。ALI组和D组尾静脉注射LPS5mg／kg制备大鼠急性肺损伤模型，C组给予等容量生理盐水，D组于注射LPS前30min时腹腔注射地塞米松6mg／kg。C组于注射生理盐水后1h（T1）时，Au组和D组分别于注射LPS后1、3和6h（T1）时，随机处死8只大鼠，取肺组织，检测MKP-1和磷酸化p38丝裂原活化蛋白激酶MAKP（p．p38MAPK）的表达。T1时回收支气管肺泡灌洗液（BALF），测定蛋白和TNF-α的浓度；观察肺组织病理学结果。另取32只SD大鼠，体重180—230g，采用随机数字表法，将其随机分为2组（n=16）：急性肺损伤组（ALI，组）和地塞米松组（D1组），处理方法同上。观察48h内大鼠生存情况。结果与C组比较，AU组BALF中蛋白和TNF—α的浓度升高，T1-3时p-p38MAKP表达上调，T2,3时MKP-1表达下调，D组BALF中TNF-α浓度升高，T1-3时p-p38MAKP和MKP-1表达上调（P〈0．05）；与Au组比较，D组BALF中蛋白和TNF．n的浓度下降，T1-3时P．p38MAKP表达下调，MKP-1表达上调（P〈0．05），病理学损伤减轻。D1组大鼠生存率高于ALI，组（P〈0．05）。结论地塞米松减轻大鼠内毒索性急性肺损伤的机制与上调肺组织MKP-1的表达，抑制p38MAPK的磷酸化，降低炎性反应有关。Objective To investigate the effect of dexamethasone on mitogen-activated protein kinase phosphatase-1 （MKP-1） expression in lung tissues in rats with lipopolysaccharide （LPS）-induced acute lung injury （ALl） .Methods Fifty-four male SD rats weighing 180-230 g were randomly divided into 3 groups： control group （group C, n = 6） ; ALI group （n = 24） and dexamethasone group （group D, n = 24）. LPS 5 mg/kg was injected via tail vein in groups ALI and D, while the equal volume of normal saline was given in group C. Dexamethasone 6 mg/kg was injected intraperitoneally at 30 min before LPS administration in group D. Eight rats in each group were sacrificed at 1 h after normal saline administration （T1） in group C and at 1, 3, and 6 h after LPS administration （T1-3 ） in groups ALl and D. The lung tissues were then removed for determination of the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38MAPK） and MKP-1 .＇ The concentrations of albumin and TNF-α in bronchoalveolar lavage fluid （BALF） were detected and histopathological changes were observed at T3 . Another 32 SD rats weighing 180-230 g were randomly divided into 2 groups （ n = 16 each） ： group ALI, and group D1 . The rats were treated as the method mentioned above and the 48 h survival condition was observed. Results Compared with group C, the concentrations of protein and TNF-a in BALF were significantly increased, p-p38MAKP expression was up-regulated at T1-3 , and MKP-1 expression was down-regulated at T2,3 in group ALI, and TNF-α concentration in BALF was significantly increased and the expression of p-p38MAKP and MKP-1 was up-regulated at T1-3 in group D （ P 〈 0.05）. Compared with group ALI, the concentrations of protein and TNF-α in BALF were significantly decreased, p-p38MAKP expression was down-regulated and MKP-1 expression was up-regulated at T1-3 （ P 〈 O. 05 ）, and the pathological damage was attenuated in group D. The 48 h survival rate was significantly higher in gro

关 键 词：地塞米松 呼吸窘迫综合征 成人 内毒素类 丝裂原活化蛋白激酶磷酸酶-1 肺 

分 类 号：R965[医药卫生—药理学]