氢气对脓毒症小鼠肺组织Nrf2/ARE通路的影响  

Effects of hydrogen on nuclear factorE2-related factor 2/antioxidant response element pathway in lung tissues in septic mice

作　　者：李媛[1] 谢克亮[1] 陈红光[1] 王卫娜[1] 王国林[1] 于泳浩[1] 

机构地区：[1]天津医科大学总医院麻醉科天津市麻醉学研究所300052

出　　处：《中华麻醉学杂志》2014年第7期852-855,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81071533,81101409,81372033）;天津市自然科学基金（11JCYBJCl2900.13JCQNJCll400）;天津市卫生局资助项目（2011KZl08）

摘　　要：目的 评价氢气对脓毒症小鼠肺组织核因子E2相关因子2（Nrf2）/抗氧化反应原件（ARE）通路的影响.方法 雄性ICR小鼠72只,体重20～ 25 g,6周龄,采用随机数字表法,将其分为4组（n=18）：假手术组（SH组）、氢气组（H2组）、脓毒症组（S组）和脓毒症＋氢气组（S＋H2组）.采用盲肠结扎穿孔 （CLP）法制备脓毒症模型.于CLP术后1和6h时H2组和S＋H2组吸入2％氢气1h.分别于CL术后7、12和24 h时各处死6只小鼠,取肺组织,采用Western blot法测定Nrf2和血红素氧合酶-1（HO-1）的蛋白表达,采用RT-PCR法检测Nrf2 mRNA的表达;于CLP术后24 h时测定肺组织病理学损伤评分和湿重/干重比值（W/D比值）,采用Western blot法测定肺组织高迁移率族蛋白B1（HMGB1）表达.结果 与SH组比较,S组和S＋H2组肺组织病理学损伤评分和W/D比值升高,Nrf2蛋白及其mRNA、HO-1和HMGB1的表达上调（P＜0.05）,H2组上述各指标差异无统计学意义（P＞0.05）;与S组比较,S＋H2组肺组织病理学损伤评分和W/D比值降低,Nrf2蛋白及其mRNA、HO-1的表达上调,HMGB1表达下调（P＜0.05）.结论 氢气减轻脓毒症小鼠急性肺损伤的机制与激活Nrf2/ARE通路有关.Objective To evaluate the effects of hydrogen （H2） on nuclear factorE2-related factor 2 （Nrf2）/antioxidant response element （ARE） pathway in lung tissues in septic mice.Methods Seventy-two male ICR mice,weighing 20-25 g,aged 6 weeks,were randomly divided into 4 groups （n =18 each） using a random number table：sham operation group （group SH）,group H2,sepsis group （group S）,and sepsis ＋ H2 group （group S ＋ H2）.Sepsis was produced by cecal ligation and puncture （CLP）.H2 and S ＋ H2 groups inhaled 2% H2 for 1 h starting from 1 and 6 h after CLP.Six mice in each group were chosen and sacrificed at 7,12 and 24 h after CLP （T1-3）.The pulmonary specimens were obtained to determine the expression of Nrf2 and HO-1 protein （by Western blot） and Nrf2 mRNA （by RT-PCR）.At 24 h after CLP,the pathological changes of lungs were scored,wet/dry lung weight ratio （W/D ratio） was determined,and the expression of high mobility group box-1 （HMGB-1） in lung tissues was measured （by Western blot）.Results Compared with group SH,the pathological scores and W/D ratio were significantly increased,and the expression of Nrf2 protein and mRNA,HO-1 and HMGB1 was up-regulated in S and S ＋ H2 groups,while no significant change was found in the indexes mentioned above in group H2.Compared with group S,the pathological scores and W/D ratio were significantly decreased,the expression of Nrf2 protein and mRNA and HO-1 was up-regulated and HMGB1 expression was down-regulated in group S ＋ H2.Conclusion The mechanism by which H2 reduces acute lung injury in septic mice is related to activation of Nrf2/ARE pathway.

关 键 词：氢 脓毒症 NF-E2相关因子2 反应元件 

分 类 号：R459.7[医药卫生—急诊医学]