摘要
目的 评价吸入氢气对脓毒症小鼠脑损伤的影响.方法 雄性ICR小鼠180只,6-8周龄,体重20 - 25 g,采用随机数字表法分为4组(n=45):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)法制备小鼠脓毒症模型.于CLP术后1和6h时H2组和CLP+H2组分别吸入2%氢气1h.分别于CLP术后7、12和24 h时,各组处死6只小鼠,取脑组织,测定伊文氏蓝(EB)含量和含水量.分别于CLP术后7、12和24h时,各组取6只小鼠,下腔静脉取血样后处死,取脑组织,采用ELISA法检测血清和脑组织TNF-α、高迁移率族蛋白B1(HMGB1)和IL-10的水平.于CLP术后24 h时,各组处死3只小鼠,取脑组织,光镜下观察海马CA1区病理学改变;各组处死6只小鼠,取脑组织,采用Western blot法测定核因子E2相关因子-2(Nrf2)和血红素氧合酶-1(HO-1)的表达.结果 与SH组比较,CLP术后7、12和24h时S组及CLP+ H2组脑组织EB含量和含水量增加,血清和脑组织TNF-α、HMGB1和IL-10的水平升高,CLP术后24h时脑组织Nrf2和HO-1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,CLP术后7、12和24 h时CLP+ H2组脑组织EB含量和含水量降低,血清和脑组织TNF-α和HMGB1的水平降低,IL-10水平升高,CLP术后24 h时脑组织Nrf2和HO-1的表达上调(P<0.05),病理学损伤减轻.结论 吸入氢气可减轻脓毒症小鼠脑损伤,其机制与激活Nrf2/ARE信号通路,抑制炎性反应有关.
Objective To evaluate the effect of hydrogen (H2) inhalation on brain injury in septic mice.Methods One hundred and eighty male ICR mice,aged 6-8 weeks,weighing 20-25 g,were randomly divided into 4 groups (n =45 each) using a random number table:sham operation group (SH group),H2 group,sepsis group (S group) and sepsis + H2 group (S + H2 group).Sepsis was produced by cecal ligation and puncture (CLP) in chloral hydrate-anesthetized mice.H2 and S + H2 groups inhaled 2% H2 for 1 h starting from 1 and 6 h after CLP.At 7,12 and 24 h after CLP,6 mice in each group were sacrificed and brains were removed for determination of Evans Blue (EB) and water contents in brain tissues.Another 6 mice in each group were chosen at 7,12 and 24 h after CLP,blood samples were obtained,the mice were then sacrificed and brains were removed to measure the concentrations of tumor necrosis factor-α (TNF-α),high mobility group protein B1 (HMGB1) and interleukin-10 (IL-10) in serum and brain tissues by ELISA.Three mice in each group were sacrificed at 24 h after LPS and brains were removed for microscopic examination of pathological changes in hippocampal CA1 region.Six mice in each group were sacrificed at 24 h after LPS and brains were removed for determination of the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in brain tissues by Western blot.Results Compared with SH group,the contents of EB and water in brain tissues were significantly increased,and the levels of TNF-α,HMGB1 and IL-10 in serum and brain tissues were increased at 7,12 and 24 h after CLP,and the expression of Nrf2 and HO-1 in brain tissues was up-regulated at 24 h after CLP in S and CLP + H2 groups,and no significant difference was found in the index above in H2 group.Compared with S group,the contents of EB and water in brain tissues were significantly decreased,the levels of TNF-α and HMGB1 in serum and brain tissues were decreased and the level of IL-10 in serum and br
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2014年第8期982-985,共4页
Chinese Journal of Anesthesiology
基金
国家自然科学基金(81071533,81101409)
天津市应用基础及前沿技术研究计划资助(11JCYBJC12900)
天津市卫生局资助项目(2011KZ108)
关键词
氢气
脓毒症
脑损伤
Hydrogen
Sepsis
Brain injuries