活化蛋白-1在大鼠内毒素性肺损伤时血红素加氧酶-1上调中的作用  

Role of activator protein-1 in up-regulation of heme oxygenase-1 expression during lipopolysaccharide-induced acute lung injury in rats

作　　者：吴丽丽[1] 余剑波[2] 宫丽荣[2] 王曼[2] 董树安[2] 李莉[2] 曹新顺[2] 刘大全[3] 

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9期1146-1149,共4页Chinese Journal of Anesthesiology

基　　金：天津市科技支撑计划项目（12ZCZDSY03300）;天津市应用基础及前沿技术研究计划（11JCYBJC11000）;天津市卫牛局科技基金（2010kz39）

摘　　要：目的评价活化蛋白-1（AP-1）在大鼠内毒索性肺损伤时血红素加氧酶-1（HO-1）上调中的作用。方法健康清洁级雄性sD大鼠48只，体重200～220g，2．5～3．0月龄，采用随机数字表法，将其随机分为4组（n=12）：正常对照组（C组）腹腔注射0．1％二甲基亚砜（姜黄素溶媒）0．5ml，30min时股静脉注射生理盐水（LPS溶媒）O．5ml；内毒素性肺损伤组（ALI组）腹腔注射0．1％二甲基亚砜0．5ml，30min时股静脉注射10mg／kgLPS0．5ml；姜黄素＋内毒素性肺损伤组（Cur＋Au组）腹腔注射20mg／kg姜黄素0．5ml，30min时股静脉注射10mg／kgLPS0．5ml；姜黄素组（Cur组）腹腔注射姜黄素20mg／kg，30min时股静脉注射生理盐水0．5ml。静脉注射LPS6h时处死大鼠取肺组织，行病理学评分，测定MDA含量和SOD活性；采用Westernblot法测定HO-1和AP-1表达；采用荧光定量PCR法测定HO-1 mRNA表达。结果与C组比较，Au组和Cur＋ALI组肺组织病理学评分和MDA含量升高，SOD活性降低，HO-1mRNA、HO-1和AP-1表达上调（P〈0．05），Cur组上述各指标差异无统计学意义（P〉0．05）；与ALI组比较，Cur＋Au组肺组织病理学评分和MDA含量升高，SOD活性降低，HO-1mRNA、HO-1和AP-1表达下调（P〈0．05）。结论内毒素性肺损伤时HO—1上调的机制与转录因子AP-1活化有一定关系。Objective To evaluate the role of activator protein- 1 （ AP- 1 ） in the up-regulation of heine ox- ygenase- 1 （ HO-1 ） expression during lipopolysaceharide （ LPS）-induced acute lung injury （ALl） in rats. Methods Forty-eight healthy male Sprague-Dawley rats, weighing 200-220 g, aged 2.5-3.0 months, were randomly di- vided into 4 groups （ n = 12 each） ： normal control group （group C）, ALl group, cureumin ＋ ALl group （group Cur＋ ALl）, and eureumin group （group Cur）. In groups C and ALl, normal saline 0.5 ml and LPS 10 mg/kg （0.5 ml） were injected intravenously, respectively, 30 rain after 0.1% dimethyl sulfoxide （the vehicle for cureu- rain） 0.5 ml was injected intraperitoneally. In groups Cur＋ ALl and Cur, cureumin 20 mg/kg （0.5 ml） was in- jected intraperitoneally, and 30 min later LPS 10 mg/kg and normal saline 0.5 ml were injected, respectively. The rats were then sacrificed at 6 h after injection of LPS. The lungs were removed for microscopic examination.＂ The pathological changes of the lung were scored. The malondialdehyde （MDA） content, superoxide dismutase （SOD） activity and expression of HO-1, AP-1 and HO-1 mRNA in lung tissues were determined. Results Compared with group C, the pathological score and MDA content were significantly increased, the SOD activity was significantly decreased, and the expression of HO-I, AP-1 and HO-1 mRNA was up-regulated in groups ALl and Cur ＋ALI （P 〈 0.05）, and no significant change was found in the parameters mentioned above in group Cur （P 〉 0.05）. The pathological score and MDA content were significantly higher, and the SOD activity and expression of HO-1, AP-I and HO-I mRNA were significantly lower in group Cur ＋ ALl than in group ALl （P 〈 0.05）. Conclusion Transcription factor AP-1 activation is involved in the up-regulation of HO-l expression during LPS-induced ALl in rats.

关 键 词：转录因子AP-1 内毒素血症 血红素加氧酶-1 呼吸窘迫综合征 成人 

分 类 号：R285.5[医药卫生—中药学]