糖皮质激素受体在大鼠内毒素性急性肺损伤中的作用  

Role of glucocorticoid receptor in acute lung injury induced by lipopolysaccharide in rats

作　　者：成勤[1] 郁峰[1] 戴志华[2] 陈龙 刘苏[4] 张茂银[4] 张稳稳[4] 刘功俭[4] 

机构地区：[1]江苏省海门市人民医院麻醉科,226100 [2]江苏省海门市人民医院急救中心,226100 [3]江苏省徐州市第六人民医院麻醉科 [4]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

出　　处：《中华麻醉学杂志》2013年第1期95-98,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：目的评价糖皮质激素受体（GR）在大鼠内毒素性急性肺损伤中的作用及可能机制。方法成年雄性sD大鼠60只，体重180～230g，采用随机数字表法，将其随机分为4组：对照组（C组，n=6）、RU486组（GR特异性拮抗剂组，R组，n=6）、急性肺损伤组（ALI组，n=24）、RU486＋Au组（RA组，n=24）。Au组尾静脉注射内毒素（LPS）5mg／kg制备大鼠急性肺损伤模型，C组给予等容量生理盐水，R组皮下注射GR拮抗剂RU48620mg／kg，RA组注射RU48620mg／kg90min后注射LPS。ALI组及RA组分别于注射LPS后1、3和6h（T1-3）时，各组随机取8只大鼠，C组与R组于注射生理盐水、RU4861h后处死取肺，检测p-p38MAPK、丝裂原活化蛋白激酶磷酸酶-1（MKP-1）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；计算细胞凋亡指数；观察肺组织病理学结果。另取32只大鼠，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（ALI1组）、RU486＋ALI组（RA，组），处理方法同上。观察48h内大鼠生存情况。结果与c组相比，ALI组、RA组BALF蛋白浓度和TNF—d浓度、细胞凋亡指数升高（P〈0．05）、病理学损伤加重；T1-3时p-p38MAPK表达上调，ALI组T2，时MKP-1表达下调，RA组T1-3，时MKP-1表达下调（P〈0．05）；与ALI组相比，RA组BALF蛋白浓度和TNF—α浓度、细胞凋亡指数增加，T1-3时p-p38MAPK表达上调（P〈0．05），T2，时MKP-1表达差异无统计学意义（P〉0．05），RA1组大鼠生存率低于ALI1组（P〈0．05）。结论GR参与大鼠内毒素急性肺损伤的发生发展，其机制与抑制p38MAPK信号转导通路，降低肺组织细胞凋亡有关。Objective To evaluate the role of glucocorticoid receptor （GR） in acute lung injury （ALI） induced by Lipopolysaccharide （LPS） in rats. Methods Sixty male Sprague-Dawley rats, weighing 180-230 g, were randomly divided into 4 groups： control group （group C, n = 6） ; GR specific inhibitor RU486 group （group R, n = 6） ; ALl group （ n = 24） ; RU486 ＋ ALI group （group RA, n = 24）. ALI was induced by injection of LPS 5 mg/kg via the tail vein in groups ALI and RA, while the equal volume of normal saline was given in group C and RU486 20 mg/kg was injected subcutaneously in group R. RU486 20 mg/kg was injected subcutaneously 90 min before LPS administration in group RA, Eight rats were chosen at 1, 3, and 6 h after LPS administration （T1-3） in groups ALI and RA and at 1 h after normal saline or Rug86 administration in groups C and R and sacrificed. The lungs were removed for determination of the expression of phosphorylated p38 mitogen-activated protein kinase （p- p38MAPK） and mitogen-activated protein kinase phosphatase-1 （MKP-1） in lung tissues. The concentrations of al- bumin and TNF〈t in bronchoalveolar lavage fluids （BALF） were detected, histopathological changes in lung tissues were observed and apoptosis index （AI） was calculated at T3 . Another 32 Sprague-Dawley rats, weighing 180-230 g, were randomly divided into 2 groups （ n = 16 each） ： group ALII and group RA1 . The rats were treated as the method mentioned above and observed for the 48 h survival rate. Results Compared with group C, the concentrations of protein and TNF-α in BALF and AI were significantly increased, the histopathological damage was aggravated, and p-p38MAKP expression was up-regulated at T1-3 in groups ALl and RA, and MKP-1 expression was downregulated at T2.3 in group ALI and at T1-3 in group RA （ P 〈 0.05）. Compared with group ALI, the concentrations of protein and TNF-a in BALF and AI were significantly increased, p-p38MAKP expression was up-regulated at T,3 （ P 〈 0.05

关 键 词：受体 糖皮质激素 呼吸窘迫综合征 成人 内毒素类 P38丝裂原活化蛋白激酶 肺 

分 类 号：R285.5[医药卫生—中药学]