吸入氢气对脓毒血症大鼠急性肺损伤的影响

Effect of hydrogen inhalation on acute lung injury in rats with sepsis

目的探讨吸入氢气（H2）对脓毒血症大鼠急性肺损伤的影响。方法选取雄性SD大鼠40只，体重200～250g。采用随机数字表法将其分为4组（n=10）：假手术组（SH组）、盲肠结扎穿孔组（CLP组）、1％H2组和2％H2组。采用CLP法制备脓毒血症模型。1％H2组与2％H2组于CLP术后12h分别吸入1％H2与2％H2 2h。结束后，采集股动脉血样行血气分析，计算氧合指数（PaO2／FiO2）；测定血浆中高迁移率族蛋白1（HMGB1）、白细胞介素-6（IL-6）水平；随后处死大鼠取肺组织，检测肺组织中Toll样受体4（TLR-4）、核因子-κB（NF—κB）、髓过氧化物酶（MPO）活性；光镜下观察肺组织病理改变。结果与sH组比较，CLP组、1％H2组、2％H2组PaO2／FiO2降低，血浆中HMGB1、IL-6水平升高，肺组织TLR-4、NF—κB、MPO水平升高，病理学损伤明显加重（P〈0．05）。与CLP组比较，1％H2组、2％H2组PaO2/FiO2升高，血浆中HMGB1、IL-6水平降低，肺组织TLR-4、NF—κB、MPO水平降低，病理学损伤也减轻（P〈0．05），1％H2组和2％H2组上述各指标组间比较差异无统计学意义（P〉0．05）。结论吸入H2能够减轻脓毒血症引起的急性肺损伤，其机制可能与抑制炎性反应有关。

Objective To investigate the effect of hydrogen （H2） inhalation on acute lung injury in rats with sepsis. Methods Forty healthy male SD rats （weighing 200-250 g） were randomly divided into 4 groups （n = 10） using a ran- dom number table： sham operation group （SH group）, cecal ligation and puncture group （CLP group）, 1% H2 group, 2% H2 group respectively. Sepsis model was produced by CLP. 1% H2 and 2% H2 group received 2 h inhalation of 1% H2 and 2% H2 at 12 h after CLP, respectively. At the end of hydrogen inhalation, blood samples were obtained for blood gas analysis. PaO2/FiO2 was calculated and the levels of high mobility group protein 1 （HMGB1）, interleukin-6 （IL-6） were determined. The rats were then sacrificed and lungs were immediately removed for determination of the activity of Toll-like receptors-4 （TLR-4）, nuclear factor kappa B （NF-κB） and myeloperoxidase （MPO）; pathology assessment of lung was done under light microscope. Results Compared with SH group, PaO2/FiO2 was significantly decreased, plasma levels of HMGB1, IL-6 increased, levels of TLR-4, NF-κB, MPO in lungs increased, and the pathological injury was significantly aggravated in CLP group, 1% H2 group and 2% H2 group （P 〈 0.05）. Compared with CLP group, PaO2/FiO2 increased significantly, levels of HMGB1, IL-6 in plasma decreased markedly, levels of TLR-4, NF-κB, MPO in lungs decreased, and the pathological injury was reduced in 1% H2 group and 2% HE group （P 〈 0.05）. There were no significant differences of the above indexes between 1% H2 group and 2% H2 group （P 〉 0.05）. Conclusion Hydrogen inhalation can alleviate sepsis induced ALI in rats, and its mechanism may be related to inhibiting inflammatory response.