Nrf2-A RE 通路与内毒素休克诱发兔急性肺损伤的关系  

Relationship between Nrf2-ARE pathway and acute lung injury induced by endotoxic shock in rabbits

作　　者：郑丹[1] 余剑波[1] 宫丽荣[1] 王曼[1] 徐妍[1] 张圆[1] 李莉[1] 曹新顺[1] 刘大全[2] 

机构地区：[1]天津市南开医院麻醉科,300100 [2]天津市中西医结合急腹症研究所

出　　处：《中华麻醉学杂志》2014年第3期334-337,共4页Chinese Journal of Anesthesiology

基　　金：天津市自然基金（11JCYBJC11000）；天津市科技支撑计划重点项目

摘　　要：目的：评价转录因子NF-E2相关因子2（Nrf2）-抗氧化反应序列元件（ARE ）通路与内毒素休克诱发兔急性肺损伤的关系。方法健康雄性新西兰大白兔30只，体重1.5～2.0 kg ，2月龄，采用随机数字表法，将其分为3组（ n＝10）：对照组（C组）、急性肺损伤组（ALI组）和全反式维甲酸组（ATRA组）。ATRA组腹腔注射Nrf2-ARE通路阻断剂全反式维甲酸6 mg/kg （过滤灭菌的植物油稀释至1.2 ml ），1次/d ，连续2 d。最后一次给药后10 h时，ALI组和ATRA组耳缘静脉注射脂多糖5 mg/kg （溶于2 ml生理盐水）制备内毒素休克诱发急性肺损伤模型，C组耳缘静脉注射生理盐水2 ml。耳缘静脉注射脂多糖或生理盐水后6h时，处死兔，取肺组织，光镜下行病理学损伤评分，测定肺湿重/干重（W/D ）比值、Nrf2 mRNA及其核蛋白、HO-1 mRNA及其蛋白的表达。结果与C组比较，ALI组和ATRA组肺组织病理学损伤评分和W/D比值升高，Nrf2 mRNA及其核蛋白、HO-1 mRNA及其蛋白的表达上调（ P＜0.05）；与ALI组比较，ATRA组肺组织病理学损伤评分和W/D比值升高，HO-1 mRNA及其蛋白表达下调（ P＜0.05），Nrf2 mRNA及其核蛋白表达差异无统计学意义（ P＞0.05）。结论 Nrf2-ARE通路激活是兔内毒素休克诱发急性肺损伤时机体的适应性调节机制。Objective To evaluate the relationship between erythroid 2-related factor （Nrf2 ）-antioxidant response element （ARE） pathway and acute lung injury （ALI） induced by endotoxic shock in rabbits .Methods Thirty healthy male New Zealand white rabbits ,aged 2 months ,weighing 1.5-2.0 kg ,were randomly divided into 3 groups （n=10 each） using a random number table ：control group （group C） ,group ALI and all-trans retinoic acid group （group ATRA ） .In group ATRA ,all-trans retinoic acid 6 mg/kg （in filter sterilized vegetable oil 1.2 ml） was injected intraperitoneally once a day for 2 days .ALI was induced by lipopolysaccharide 5 mg/kg （in normal saline 2 ml ） injected via the auricular vein at 10 h after the last injection of ATRA in ALI and ATRA groups .The equal volume of normal saline was injected instead in group C .The rabbits were sacrificed at 6 h after lipopolysaccharide or normal saline administration .The pulmonary specimens were removed for determination of wet/dry lung weight ratio （W/D ratio ） and expression of Nrf2 mRNA and nuclear protein ,and HO-1 mRNA and protein in lung tissues .The pathological changes of lungs were scored .Results Compared with group C ,the pathological score and W/D ratio were significantly increased , and the expression of Nrf2 mRNA and nuclear protein ,and HO-1 mRNA and protein was up-regulated in ALI and ATRA groups （ P 0.05 ） .Conclusion Activation of Nrf2-ARE pathway is the regulatory mechanism of the body adapting to the ALI induced by endotoxic shock in rabbits .

关 键 词：NF-E2相关因子2 反应元件 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]