Division of Pulmonary Immunology and Infectious Diseases, Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan.
Transl Res. 2011 Jul;158(1):17-29. doi: 10.1016/j.trsl.2011.02.002. Epub 2011 Mar 1.
Apocynin suppresses the generation of reactive oxygen species (ROS) that are implicated in ischemia-reperfusion (I/R) lung injury. We thus hypothesized that apocynin attenuates I/R. Furthermore, we explored the mechanisms by which apocynin may attenuate I/R. I/R was induced in an isolated and perfused rat lung model with ischemia for 1 h followed by reperfusion for 1 h. Apocynin was administered in the circulating perfusate at the onset of ischemia. Hemodynamics, lung injury indices, inflammatory responses, and activation of apoptotic pathways were determined. An increase in lung permeability and lung weight gain was noted after I/R. Peak airway pressure was increased, and pH of circulating perfusate was decreased. The adhesion molecule of neutrophil (CD31) in perfusate was upregulated. The levels of albumin, white blood cell count, and inflammatory cytokines including interleukin-1β, tumor necrosis factor-α, and macrophage inflammatory protein-2 increased in lung lavage fluid; the concentrations of carbonyl and thiobarbituric acid reactive substances were greater in the circulating perfusate; and the expression of myeloperoxidase, JNK, P38, and caspase-3 in lung tissue was greater in the control group. Upregulation and activation of nuclear factor-κB (NF-κB) in nuclei were found in I/R. The administration of apocynin attenuated these inflammatory responses and lung permeability associated with decreased activation of NF-κB. We conclude that I/R is associated with inflammatory responses including the generation of ROS, adhesion protein of neutrophil, cytokines, and the activation of mitogen-activated protein kinase and NF-κB cascade. The administration of apocynin attenuates the inflammatory responses and I/R in the isolated, perfused rat lung model.
阿朴肉桂酸抑制活性氧（ROS）的产生，ROS 被认为与缺血再灌注（I/R）肺损伤有关。因此，我们假设阿朴肉桂酸可以减轻 I/R。此外，我们还探讨了阿朴肉桂酸减轻 I/R 的机制。在离体灌注大鼠肺模型中，通过缺血 1 小时后再灌注 1 小时来诱导 I/R。阿朴肉桂酸在缺血开始时给予循环灌流液中。测定血流动力学、肺损伤指数、炎症反应和凋亡途径的激活。I/R 后，肺通透性增加，肺重量增加。气道峰压升高，循环灌流液 pH 值降低。灌洗液中中性粒细胞黏附分子（CD31）上调。肺灌洗液中白蛋白、白细胞计数和炎症细胞因子（包括白细胞介素-1β、肿瘤坏死因子-α和巨噬细胞炎症蛋白-2）的水平升高；循环灌流液中羰基和硫代巴比妥酸反应物质的浓度更高；对照组肺组织中髓过氧化物酶、JNK、P38 和 caspase-3 的表达增加。I/R 中发现核因子-κB（NF-κB）的上调和激活。给予阿朴肉桂酸可减轻这些与 NF-κB 激活减少相关的炎症反应和肺通透性。我们得出结论，I/R 与炎症反应有关，包括 ROS 的产生、中性粒细胞黏附蛋白、细胞因子以及丝裂原激活蛋白激酶和 NF-κB 级联的激活。阿朴肉桂酸可减轻离体灌注大鼠肺模型中的炎症反应和 I/R。
