Zhang Er-Fei, Hou Zuo-Xu, Shao Tian, Yang Wan-Wan, Hu Bin, Wang Xiao-Xia, Zhang Ze-Xin, Huang Yi, Xiong Li-Ze, Hou Li-Chao
Department of Anesthesiology and Critical Care Medicine, Xijing Hospital, The Fourth Military Medical UniversityXi'an 710032, Shaanxi Province, P. R. China.
Department of Anesthesiology, The Affiliated Hospital of Yan'an UniversityYan'an 716000, Shaanxi Province, P. R. China.
Am J Transl Res. 2017 Jun 15;9(6):3105-3119. eCollection 2017.
Our study aims to investigate the effects of the inhalation of subanesthestic doses of sevoflurane combined with oxygen on sepsis. Male Sprague-Dawley rats or Male ICR/Km mice underwent caecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysccharide (LPS) to induce sepsis, while sham rats were used as control. Then, rats were treated with the inhalation of sevoflurane in oxygen; and air or 100% oxygen was used as control. Seven-day survival, lung injury and inflammatory factors were assessed. In this experiment, we obtained RAW264.7 macrophages and human peripheral blood mononuclear cells (PBMCs) incubated by LPS or plasma from septic patients to explore the NF-κB pathway in the effect of the inhalation of sevoflurane combined with oxygen in sepsis. In this study, we found that the inhalation of 0.5 MAC of sevoflurane in 60% oxygen was the best protocol for protecting against lethality resulting from sepsis and ALI, and there was a time window for these protective effects. We also founded that 0.5 MAC of sevoflurane in 60% oxygen inhibited the nuclear translocation of NF-κB in human PBMCs induced by LPS or plasma from septic patients. The subanesthesia dose sevoflurane in 60% oxygen may reduce sepsis-induced inflammatory responses in animals and in PBMCs, and the inhibition to the activation of the NF-κB pathway may contribute to this protection.
我们的研究旨在调查吸入亚麻醉剂量的七氟醚联合氧气对脓毒症的影响。雄性斯普拉格-道利大鼠或雄性ICR/Km小鼠接受盲肠结扎和穿刺(CLP)或腹腔注射脂多糖(LPS)以诱导脓毒症,而假手术大鼠用作对照。然后,大鼠接受吸入七氟醚联合氧气治疗;空气或100%氧气用作对照。评估7天生存率、肺损伤和炎症因子。在本实验中,我们获取经脂多糖或脓毒症患者血浆孵育的RAW264.7巨噬细胞和人外周血单核细胞(PBMCs),以探究吸入七氟醚联合氧气在脓毒症中的作用机制中的核因子κB(NF-κB)信号通路。在本研究中,我们发现吸入60%氧气中0.5最低肺泡有效浓度(MAC)的七氟醚是预防脓毒症和急性肺损伤(ALI)致死的最佳方案,且这些保护作用存在时间窗。我们还发现,吸入60%氧气中0.5 MAC的七氟醚可抑制脂多糖或脓毒症患者血浆诱导的人PBMCs中NF-κB的核转位。60%氧气中的亚麻醉剂量七氟醚可能减轻动物和PBMCs中脓毒症诱导的炎症反应,对NF-κB信号通路激活的抑制作用可能促成了这种保护作用。