保护剂DX后处理改善博来霉素诱导的小鼠肺纤维化和肺功能障碍
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背景与目的
保护剂DX（10S，17S-二羟基果胶-4Z，7Z，11E，13Z，15E，19Z-六烯酸）（PDX）,来自Ω-3脂肪二十二碳六烯酸，可发挥抗炎和减弱生物反应，迄今为止，其对肺纤维化的影响的研究甚少。
方 法
通过组织学分析、转化电子显微镜（TEM）、肺部羟脯氨酸含量和细胞因子测试进行评估。
结 果
我们的研究表明，PDX对肺纤维化小鼠可发挥潜在的治疗效果，这种潜在的治疗效果不同于抗炎和削弱生物反应，在本研究中，博莱霉素（BLM）作用于小鼠第7天后可增加炎症浸润，胶原沉积和导致肺功能障碍，证实PDX后处理改善了BLM诱导的炎症反应、细胞外基质（ECM）沉积以及与纤维化相关的细胞因子水平，此外，PDX改善了肺呼吸功能，纠正BLM诱导的低氧血症，并且延长寿命，另外，我们发现不管是体内实验或体外实验，PDX可逆转上皮 - 间充质转换（EMT）表型的转化，增强了促进纤维化转化的潜在机制。
结 论
总之，我们的研究结果表明用PDX后处理可以改善BLM诱导的小鼠肺纤维化和肺功能障碍，PDX是有望治疗肺纤维化疾病的药物。
原始文献摘要
Li H, Hao Y, Zhang H, et al. Posttreatment with Protectin DX ameliorates bleomycin-induced pulmonary fibrosis and lung dysfunction in mice[J]. Scientific Reports, 2017, 7.
Protectin DX (10S,17S-dihydroxydocosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic acid) (PDX), generated from Ω-3 fatty docosahexaenoic acids, is believed to exert anti-inflammatory and proresolution bioactions. To date, few studies have been performed regarding its effect on pulmonary fibrosis. Herein we show that PDX exerts a potential therapeutic effect which is distinct from its anti-inflammation and pro-resolution activity on mice with pulmonary fibrosis. In the present study, we showed that bleomycin (BLM) increased inflammatory infiltration, collagen deposition, and lung dysfunction on day7 after challenged in mice. Posttreatment with PDX ameliorated BLM-induced inflammatory responses, extracellular matrix (ECM) deposition and the level of cytokines related to fibrosis as evaluated by histology analysis, transformation electron microscope (TEM), lung hydroxyproline content and cytokines test. Moreover, PDX improved lung respiratory function, remedied BLM-induced hypoxemia and prolonged life span. In addition, we found that PDX reversed epithelial–mesenchymal transition (EMT) phenotypic transformation in vivo and in vitro, reinforcing a potential mechanism of promoting fibrosis resolution. In summary, our findings showed that posttreatment with PDX could ameliorate BLM-induced pulmonary fibrosis and lung dysfunction in mice and PDX may be considered as a promising therapeutic approached to fibrotic lung diseases.
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