St Luke's Roosevelt Hospital Center, New York, NY, USA.
Lung. 2011 Feb;189(1):51-6. doi: 10.1007/s00408-010-9271-2. Epub 2010 Dec 14.
Aerosolized hyaluronan (HA) has been previously shown to prevent cigarette smoke-induced airspace enlargement and elastic fiber injury in mice when given concurrently with smoke. In the present study, a more stringent test of the therapeutic potential of HA was performed by delaying treatment with this agent for 1 month. After treatment with cigarette smoke for 3 h per day for 5 days per week for 1 month, mice (DBA/2J) began receiving aerosolized HA (0.1%) for 1 h prior to smoke exposure (controls were given aerosolized water). The results indicate that much of the damage to the lung elastic fibers occurred within the first several months of smoke exposure, as measured by levels of desmosine and isodesmosine (DID) in bronchoalveolar lavage fluid (BALF). In contrast to previously published studies, where concurrent administration of aerosolized HA significantly reduced BALF DID levels within 3 months of smoke exposure, the same effect was not seen until 6 months when HA treatment was delayed. However, despite the prolonged breakdown of elastic fibers in the current study, a significant reduction in airspace enlargement was observed after only 2 months of HA treatment. These findings provide further support for testing this agent in patients with pre-existing chronic obstructive pulmonary disease.
雾化透明质酸（HA）先前已被证明可预防香烟烟雾引起的小鼠气道扩张和弹性纤维损伤，当与烟雾同时给予时。在本研究中，通过延迟该药物治疗 1 个月来更严格地测试 HA 的治疗潜力。在每天吸烟 3 小时，每周 5 天，1 个月后，接受雾化 HA（0.1%）治疗的小鼠（DBA/2J）在暴露于烟雾之前先进行 1 小时的雾化（对照组给予雾化水）。结果表明，正如支气管肺泡灌洗液（BALF）中的脱硫酸软骨素和异脱硫酸软骨素（DID）水平所测量的那样，在吸烟暴露的最初几个月中，肺弹性纤维的大部分损伤已经发生。与先前发表的研究不同，在吸烟暴露的 3 个月内，同时给予雾化 HA 可显著降低 BALF DID 水平，但直到 6 个月时延迟 HA 治疗时才出现这种效果。然而，尽管在当前研究中弹性纤维的分解时间延长，但仅在接受 HA 治疗 2 个月后，就观察到气道扩张的显著减少。这些发现为在患有慢性阻塞性肺疾病的患者中测试该药物提供了进一步的支持。
