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.

abstractsObjective 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.