氢气通过抑制核转录因子-κB信号通路抑制缺血再灌注急性肺损伤的炎性反应  

Hydrogen gas inhibits inflammation in acute lung injury induced by ischemia/reperfusion via inhibiting the nuclear transcription factor-κB signaling pathway

作　　者：石海梅 牛姣姣[1] 曹彬 付志杰 Shi Haimei;Niu Jiaojiao;Cao Bin;Fu Zhijie(Department of Anesthesiology,Pain and Perioperative Medicine,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院麻醉与围术期医学部,450052

出　　处：《中华实验外科杂志》2022年第6期1128-1131,共4页Chinese Journal of Experimental Surgery

摘　　要：目的探索氢气(H2)在缺血再灌注(I/R)诱导的急性肺损伤(ALI)中的抗炎作用及其机制。方法通过失血1 h, 复苏2 h制作大鼠压力控制型失血性休克复苏模型来制作I/R诱导的ALI模型。实验分为3组, 假手术组(S组)、模型组(C组)、氢气组(H组)。S、C组大鼠全程吸入60%N2-40%O2混合气, H组复苏全程吸入2%H2-58%N2-40%O2混合气, 余同C组。通过血气分析、肺干/湿比(W/D)、苏木精-伊红(HE)染色等评价H2对ALI病理改变及肺功能的影响;采用髓过氧化物酶(MPO)活性, 白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)及肺组织核转录因子(NF)-κBp65的表达评价H2对ALI炎性反应的影响。组间比较采用单因素方差分析的SNK检验或者非参数秩和检验(Kruskal Wallis秩和检验)。结果 H2可提高I/R大鼠PaO2/FiO2[C组(325±22) mmHg比H组(370±36) mmHg(1 mmHg=0.133 kPa), F=25.285, P<0.05], 减轻肺水肿[肺W/D:C组(4.94±0.14)比H组(4.75±0.12), F=8.142, P<0.05], 改善肺损伤(HE染色), 降低肺损伤评分[C组(7.50±1.07)比H组(4.50±1.07), F=62.515, P<0.05], 降低TNF-α[C组(66.58±5.17) pg/ml比H组(55.58±10.06) pg/ml, F=69.229, P<0.05]、IL-6的含量[C组(28.09±2.06) pg/ml比H组(23.50±2.77) pg/ml, F=24.542, P<0.05], 抑制MPO活性[C组(1.55±0.14) U/g湿片比H组(1.15±0.18) U/g湿片, F=154.621, P<0.05], 及NF-κBp65的表达[NF-κB p65评分:C组(5.16±1.07)比H组(2.30±0.36), F=93.938, P<0.05]。结论吸入2%H2可改善肺功能、降低肺损伤程度, 其机制可能是H2通过抑制NF-κB信号通路抑制I/R诱导的ALI的炎性反应。Objective To explore the anti-inflammatory effect of hydrogen gas(H2)on acute lung injury(ALI)induced by ischemia/reperfusion(I/R)and its possible mechanisms.Methods The ALI model induced by I/R was established by blood loss of 1 h and resuscitation of 2 h to make the pressure-controlled hemorrhagic shock resuscitation model in rats.The experiment was divided into three groups:sham operation group(group S),model control group(group C)and hydrogen group(group H).The rats in groups S and C inhaled 60%nitrogen-40%oxygen mixture throughout the whole process.The rats in group H inhaled 2%hydrogen-58%nitrogen-40%oxygen mixture throughout the resuscitation process,and the rest was the same as group C.The effects of H2 on pathological changes and lung function of ALI were evaluated by blood gas analysis,lung wet/dry(W/D)and HE staining.The effect of H2 on the inflammation of ALI was evaluated by the activity of myeloperoxidase(MPO)and expression of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and nuclear transcription factor(NF-κBp65)in lung tissue.SNK test of one-way ANOVA or nonparametric rank sum test(Kruskal Wallis rank sum test)were used for comparison between groups.Results Hydrogen improved PaO2/FiO2 from the arterial blood[group C(325±22)mmHg vs.group H(370±36)mmHg(1 mmHg=0.133 kPa),F=25.285,P<0.05],reduced pulmonary edema[lung W/D:group C(4.94±0.14)vs.group H(4.75±0.12),F=8.142,P<0.05],improved lung injury[hematoxylin and eosin(HE)staining]and decreased lung injury score[group C(7.50±1.07)vs.group H(4.50±1.07),F=62.515,P<0.05].Hydrogen decreased the contents of TNF-α[group C(66.58±5.17)pg/ml vs.group H(55.58±10.06)pg/ml,F=69.229,P<0.05]and IL-6[group C(28.09±2.06)pg/ml vs.group H(23.50±2.77)pg/ml,F=24.542,P<0.05],decreased MPO activity[group C(1.55±0.14)U/g wet tablets vs.group H(1.15±0.18)U/g wet tablets,F=154.621,P<0.05],and inhibited the expression of NF-κBp65 in lung tissues[NF-κBp65 score:group C(5.16±1.07)vs.group H(2.30±0.36),F=93.938,P<0.05].Conclusion Inhalation of 2%H2 improved

关 键 词：氢气 核转录因子-κB信号通路 缺血再灌注 急性肺损伤 炎性反应 

分 类 号：R563[医药卫生—呼吸系统]