Hydrogen Sulfide Inhalation Improves Neurological Outcome via NF-κB-Mediated Inflammatory Pathway in a Rat Model of Cardiac Arrest and Resuscitation
Hydrogen Sulfide Inhalation Improves Neurological Outcome via NF-κB-Mediated Inflammatory Pathway in a Rat Model of Cardiac Arrest and Resuscitation
复制标题
硫化氢吸入通过 NF-κB 介导的心脏骤停和复苏大鼠模型中的炎症通路改善神经系统结果
DOI：
10.1159/000430316
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Wang, Guonian
中科院分区：
文献类型：
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作者：
Wei, Xia;Zhang, Bing;Wang, Guonian
背景/目的：硫化氢对心脏骤停(CA)和心肺复苏(CPR)后脑部炎症反应的影响尚不清楚。在这项研究中，我们研究了外源性40ppm和80ppm硫化氢气体对CA/CPR后炎症反应和神经预后的影响。方法：用室颤诱发冠脉循环，然后进行心肺复苏。心肺复苏后立即吸入40或80ppm硫化氢1h。分别于心肺复苏后24 h检测各组大鼠血清IL-1、IL-6、肿瘤坏死因子-α水平、髓过氧化物酶活性、诱导型一氧化氮合酶和细胞间黏附分子-1的表达以及核因子-κB的磷酸化和转位。在CA/CPR后14d观察胶带剥离实验、存活率和海马神经元计数。结果：CA/CPR组IL-1、IL-6、TNF-α和MPO活性显著升高。NF-κB的磷酸化、易位及iNOS、ICAM-1的表达均显著增加。吸入40或80ppm的硫化氢气体可减少这些炎性细胞因子。此外，40或80ppm的硫化氢可抑制NF-κB及其下游促炎介质iNOS和ICAM-1的激活。吸入硫化氢还改善了神经功能、14d存活率，并减少了海马神经元的丢失。结论：吸入硫化氢对CA/CPR后脑损伤有保护作用。H_2S的保护作用机制可能与其通过降低IL-1？、IL-6和TNF-α水平，抑制中性粒细胞的活化和浸润，从而抑制CA/CPR诱导的炎症反应有关。硫化氢的有益作用可能是通过下调NF-κB和下游的促炎信号通路来实现的。
Background/Aims: The effects of H2S on cerebral inflammatory reaction after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remain poorly understood. In this study, we investigated the effects of exogenous 40 ppm and 80 ppm H2S gas on inflammatory reaction and neurological outcome after CA/CPR. Methods: CA was induced by ventricular fibrillation and followed by CPR. Forty or 80 ppm H2S was inhaled for 1 h immediately following CPR. The levels of IL-1ß, IL-6 and TNF-a, the myeloperoxidase (MPO) activity, the expression of iNOS and ICAM-1, and the phosphorylation and translocation of NF-κB were evaluated at 24 h after CA/CPR. The tape removal test, survival rate and hippocampal neuronal counts were investigated at 14 d after CA/CPR. Results: CA/CPR induced significant increases in IL-1ß, IL-6, TNF-a and MPO activity. The phosphorylation and translocation of NF-κB, and the expression of iNOS and ICAM-1 were increased significantly. Inhalation of 40 or 80 ppm H2S gas decreased these inflammatory cytokines. Furthermore, 40 or 80 ppm H2S inhibited the activation of NF-κB and the downstream proinflammatory mediators iNOS and ICAM-1. H2S inhalation also improved neurological function, 14-d survival rate, and reduced hippocampal neuronal loss. Conclusion: These results indicated that inhalation of H2S protected against brain injury after CA/CPR. The mechanisms underlying protective effects of H2S were associated with the inhibition of CA/CPR-induced inflammation reactions by reducing IL-1ß, IL-6 and TNF-a, and concomitantly inhibiting the activation and infiltration of neutrophils. The beneficial effects of H2S might be mediated by downregulation of NF-κB and the downstream proinflammatory signaling pathway.