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首页> 外文期刊>Physiological Reports >17(R)‐resolvin D1 ameliorates bleomycin‐induced pulmonary fibrosis in mice
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17(R)‐resolvin D1 ameliorates bleomycin‐induced pulmonary fibrosis in mice

机译：17（R）-resolvin D1改善博莱霉素诱导的小鼠肺纤维化

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AbstractIdiopathic pulmonary fibrosis (IPF) is a destructive inflammatory disease with limited therapeutic options. Inflammation plays an integral role in the development of pulmonary fibrosis. Unresolved inflammatory responses can lead to substantial tissue injury, chronic inflammation, and fibrosis. The resolvins are a family of endogenous ω-3 fatty acid derived-lipid mediators of inflammation resolution. Resolvin D1 (RvD1) displays potent anti-inflammatory, pro-resolving activity, without causing immunosuppression. Its epimer, 17(R)-resolvin D1 (17(R)-RvD1), exhibits equivalent functionality to RvD1. In addition, 17(R)-RvD1 is resistant to rapid inactivation by eicosanoid oxidoreductases. In the present study, we tested the hypothesis that 17(R)-RvD1 can provide a therapeutic benefit in IPF by reducing inflammation and pulmonary fibrosis, while leaving the normal immune response intact. Mice were exposed to bleomycin (BLM) via micro-osmotic pump to induce pulmonary fibrosis, and were then treated with 17(R)-RvD1 or vehicle by intraperitoneal injection. Administration of 17(R)-RvD1 from the start of BLM treatment attenuated neutrophil alveolar infiltration, lung collagen content, and Interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and type I collagen mRNA expression, along with subsequent reduction in histologically detectable fibrosis. The 17(R)-RvD1-induced infiltration of inflammatory cells was inhibited by an antagonist of lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2). The administration of 17(R)-RvD1 at the later fibrotic stage also improved the lung failure. These results suggest that 17(R)-RvD1 attenuates pulmonary fibrosis by promoting the resolution of neutrophilic inflammation and also provides pulmonary restoration. These data highlight the therapeutic potential of 17(R)-RvD1 in the management of this intractable disease.
机译：摘要特发性肺纤维化（IPF）是一种破坏性的炎症性疾病，治疗选择有限。炎症在肺纤维化的发展中起着不可或缺的作用。未解决的炎症反应可导致严重的组织损伤，慢性炎症和纤维化。分辨素是炎症缓解的内源性ω-3脂肪酸衍生的脂质介体家族。 Resolvin D1（RvD1）显示有效的抗炎，促分解活性，而不会引起免疫抑制。它的差向异构体17（R）-resolvin D1（17（R）-RvD1）具有与RvD1相同的功能。此外，17（R）-RvD1抵抗类花生酸氧化还原酶的快速失活。在本研究中，我们测试了17（R）-RvD1可以通过减少炎症和肺纤维化，同时保持正常的免疫应答而在IPF中提供治疗益处的假设。通过微渗透泵将小鼠暴露于博来霉素（BLM）以诱导肺纤维化，然后通过腹膜内注射用17（R）-RvD1或溶媒治疗。从BLM治疗开始就开始施用17（R）-RvD1可减轻中性粒细胞肺泡浸润，肺胶原含量和白细胞介素-1β（IL-1β），转化生长因子-β1（TGF-β1），结缔组织生长因子（CTGF） ）和I型胶原mRNA表达，以及随后在组织学上可检测到的纤维化程度降低。脂蛋白A4受体/甲酰基肽受体2（ALX / FPR2）的拮抗剂抑制17（R）-RvD1诱导的炎症细胞浸润。在随后的纤维化阶段给予17（R）-RvD1也可以改善肺衰竭。这些结果表明，17（R）-RvD1通过促进中性粒细胞炎症的消退来减轻肺纤维化，并且还提供了肺的恢复。这些数据突出了17（R）-RvD1在治疗这种顽固性疾病中的治疗潜力。

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