美国研究人员在人类及小鼠身上的试验显示，十字花科植物富含的萝卜硫素有助肺部清除有害细菌。

美国约翰斯·霍普金斯大学研究人员13日发表报告说，萝卜硫素能激活一种名为NRF2的信号通道。这种信号通道一旦不能发挥作用，人体巨噬细胞就无法清除肺部的死亡细胞及外来细菌，从而使肺部无法保持清洁，导致感染。吸烟者及慢性阻塞性肺病（慢阻肺）患者的巨噬细胞都失去了这种清理功能。

研究人员首先将43名慢阻肺患者的巨噬细胞暴露于两种细菌环境中，其中一种环境下，巨噬细胞不能发挥“清道夫”作用；而另一种环境下，巨噬细胞接受萝卜硫素治疗后，NRF2通道得以激活，巨噬细胞分辨、吞噬细菌的能力也得到修复。

研究人员随后培育了两组分别暴露于吸烟环境一周以及六个月的小鼠，它们的肺部细菌均开始增多，与人类慢阻肺患者症状类似。利用萝卜硫素治疗小鼠后，它们肺部的细菌开始逐步得到清理。研究人员发现，萝卜硫素似乎并没有刺激小鼠产生更多巨噬细胞，而是增强了现有巨噬细胞的功能。

这项研究成果13日发表在美国《科学·转化医学》杂志上。研究人员目前已开始在慢阻肺患者中进行二期临床试验，以确认萝卜硫素能否提高患者肺部功能。

萝卜硫素是常见抗氧化剂，在西兰花、芥蓝等十字花科植物中含量较丰富。

原文出处：

Science Translational Medicine, 2011; 3 (78): 78ra32 DOI: 10.1126/scitranslmed.3002042

Targeting Nrf2 Signaling Improves Bacterial Clearance by Alveolar Macrophages in Patients with COPD and in a Mouse Model

C. J. Harvey, R. K. Thimmulappa, S. Sethi, X. Kong, L. Yarmus, R. H. Brown, D. Feller-Kopman, R. Wise, S. Biswal

Patients with chronic obstructive pulmonary disease (COPD) have innate immune dysfunction in the lung largely due to defective macrophage phagocytosis. This deficiency results in periodic bacterial infections that cause acute exacerbations of COPD, a major source of morbidity and mortality. Recent studies indicate that a decrease in Nrf2 (nuclear erythroid–related factor 2) signaling in patients with COPD may hamper their ability to defend against oxidative stress, although the role of Nrf2 in COPD exacerbations has not been determined. Here, we test whether activation of Nrf2 by the phytochemical sulforaphane restores phagocytosis of clinical isolates of nontypeable Haemophilus influenza (NTHI) and Pseudomonas aeruginosa (PA) by alveolar macrophages from patients with COPD. Sulforaphane treatment restored bacteria recognition and phagocytosis in alveolar macrophages from COPD patients. Furthermore, sulforaphane treatment enhanced pulmonary bacterial clearance by alveolar macrophages and reduced inflammation in wild-type mice but not in Nrf2-deficient mice exposed to cigarette smoke for 6 months. Gene expression and promoter analysis revealed that Nrf2 increased phagocytic ability of macrophages by direct transcriptional up-regulation of the scavenger receptor MARCO. Disruption of Nrf2 or MARCO abrogated sulforaphane-mediated bacterial phagocytosis by COPD alveolar macrophages. Our findings demonstrate the importance of Nrf2 and its downstream target MARCO in improving antibacterial defenses and provide a rationale for targeting this pathway, via pharmacological agents such as sulforaphane, to prevent exacerbations of COPD caused by bacterial infection