Department of Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, 5th floor, Baltimore, MD, USA.
BMC Pulm Med. 2014 Apr 18;14:64. doi: 10.1186/1471-2466-14-64.
Pulmonary fibrosis is an untreatable, fatal disease characterized by excess deposition of extracellular matrix and inflammation. Although the etiology of pulmonary fibrosis is unknown, recent studies have implicated dysregulated immune responses and wound healing. Since n-3 polyunsaturated fatty acids (n-3 PUFAs) may beneficially modulate immune responses in a variety of inflammatory disorders, we investigated the therapeutic role of docosahexaenoic acid (DHA), a single n-3 PUFA, in lung fibrosis.
Intratracheal DHA or PBS was administered to mouse lungs 4 days prior to intratracheal bleomycin treatment. Body weight and survival were monitored for 21 days. Bronchoalveolar fluid (BALF) and lung inflammatory cells, cytokines, eicosanoids, histology and lung function were determined on serial days (0, 3, 7, 14, 21) after bleomycin injury.
Intratracheal administration of DHA mitigated bleomycin-induced lung injury. Mice pretreated with DHA had significantly less weight loss and mortality after bleomycin injury. The lungs from DHA-pretreated mice had markedly less fibrosis. DHA pretreatment also protected the mice from the functional changes associated with bleomycin injury. Bleomycin-induced cellular inflammation in BALF and lung tissue was blunted by DHA pretreatment. These advantageous effects of DHA pretreatment were associated with decreased IL-6, LTB4, PGE2 and increased IL-10.
Our findings demonstrate that intratracheal administration of DHA, a single PUFA, protected mice from the development of bleomycin-induced pulmonary inflammation and fibrosis. These results suggest that further investigations regarding the role of n-3 polyunsaturated fatty acids in fibrotic lung injury and repair are needed.
肺纤维化是一种无法治愈的致命疾病，其特征是细胞外基质过度沉积和炎症。虽然肺纤维化的病因尚不清楚，但最近的研究表明，免疫反应失调和伤口愈合异常与肺纤维化有关。由于 n-3 多不饱和脂肪酸（n-3 PUFAs）可能在多种炎症性疾病中有益地调节免疫反应，我们研究了二十二碳六烯酸（DHA）作为单一 n-3 PUFA 在肺纤维化中的治疗作用。
在气管内博来霉素治疗前 4 天，向小鼠肺部给予 DHA 或 PBS。监测 21 天的体重和存活率。在博来霉素损伤后连续几天（0、3、7、14、21）测定支气管肺泡灌洗液（BALF）和肺炎性细胞、细胞因子、类二十烷酸、组织学和肺功能。
气管内给予 DHA 减轻了博来霉素引起的肺损伤。经 DHA 预处理的小鼠在博来霉素损伤后体重减轻和死亡率明显降低。DHA 预处理的小鼠肺部纤维化明显减少。DHA 预处理还保护了小鼠免受博来霉素损伤相关的功能变化。DHA 预处理可减轻博来霉素诱导的 BALF 和肺组织中细胞炎症。DHA 预处理的这些有利作用与 IL-6、LTB4、PGE2 减少和 IL-10 增加有关。
我们的研究结果表明，气管内给予 DHA（一种单一的 PUFA）可保护小鼠免受博来霉素诱导的肺炎症和纤维化的发生。这些结果表明，需要进一步研究 n-3 多不饱和脂肪酸在纤维性肺损伤和修复中的作用。
