C16 peptide and angiopoietin-1 (Ang-1) have been found to have anti-inflammatory activity in various inflammation-related diseases. However, their combined role in acute respiratory distress syndrome (ARDS) has not been investigated yet. The objective of this study was to investigate the effects of C16 peptide and Ang-1 in combination with lipopolysaccharide (LPS)-induced inflammatory insult in vitro and in vivo. Human pulmonary microvascular endothelial cells and human pulmonary alveolar epithelial cells were used as cell culture systems, and an ARDS rodent model was used for in vivo studies. Our results demonstrated that C16 and Ang-1 in combination significantly suppressed inflammatory cell transmigration by 33% in comparison with the vehicle alone, and decreased the lung tissue wet-to-dry lung weight ratio to a maximum of 1.53, compared to 3.55 in the vehicle group in ARDS rats. Moreover, C + A treatment reduced the histology injury score to 60% of the vehicle control, enhanced arterial oxygen saturation (SO₂), decreased arterial carbon dioxide partial pressure (PCO₂), and increased oxygen partial pressure (PO₂) in ARDS rats, while also improving the survival rate from 47% (7/15) to 80% (12/15) and diminishing fibrosis, necrosis, and apoptosis in lung tissue. Furthermore, when C + A therapy was administered 4 h following LPS injection, the treatment showed significant alleviating effects on pulmonary inflammatory cell infiltration 24 h postinsult. In conclusion, our in vitro and in vivo studies show that C16 and Ang-1 exert protective effects against LPS-induced inflammatory insult. C16 and Ang-1 hold promise as a novel agent against LPS-induced ARDS. Further studies are needed to determine the potential for C16 and Ang-1 in combination in treating inflammatory lung diseases.

Impact statement

The mixture of C16 peptide and Ang-1 is a novel therapeutic agent, which has been confirmed as effective in several inflammatory diseases of central nervous system in previous studies. Since this compound medicine has a general role in protecting against inflammation and edema, its acting mechanisms may be not tissue- or organ-specific, and it may provide a valuable clue to the potential clinical application in the prevention and treatment of inflammatory lung diseases like ARDS. The experimental research of the novel therapeutic agent’s potential protective effects in different animal models will be beneficial for the future drug transformation and clinical trial.

中文翻译：

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C16肽和血管生成素-1化合物在脂多糖诱导的急性呼吸窘迫综合征中的保护作用。

已发现 C16 肽和血管生成素-1 (Ang-1) 在各种炎症相关疾病中具有抗炎活性。然而，尚未研究它们在急性呼吸窘迫综合征 (ARDS) 中的综合作用。本研究的目的是在体外和体内研究 C16 肽和 Ang-1 与脂多糖 (LPS) 诱导的炎症损伤的联合作用。以人肺微血管内皮细胞和人肺泡上皮细胞为细胞培养系统，采用ARDS啮齿动物模型进行体内学习。我们的结果表明，与单独的载体相比，C16 和 Ang-1 的组合显着抑制了 33% 的炎性细胞迁移，并将肺组织的湿肺重量比降低至 1.53，而在对照组中为 3.55。 ARDS 大鼠中的载体组。此外，C + A 治疗将组织学损伤评分降低至载体对照的 60%，提高了动脉血氧饱和度 (SO ₂ )，降低了动脉二氧化碳分压 (PCO ₂ )，并增加了氧分压 (PO ₂) 在 ARDS 大鼠中，同时还将存活率从 47% (7/15) 提高到 80% (12/15) 并减少肺组织的纤维化、坏死和细胞凋亡。此外，当在 LPS 注射后 4 小时给予 C+A 治疗时，该治疗显示出对损伤后 24 小时肺部炎症细胞浸润的显着缓解作用。总之，我们的体外和体内研究表明 C16 和 Ang-1 对 LPS 诱导的炎症损伤发挥保护作用。C16 和 Ang-1 有望成为对抗 LPS 诱导的 ARDS 的新型药物。需要进一步的研究来确定 C16 和 Ang-1 联合治疗炎症性肺病的潜力。

影响陈述

C16肽与Ang-1的混合物是一种新型治疗剂，在以往的研究中已证实对多种中枢神经系统炎症性疾病有效。由于该复方药物具有预防炎症和水肿的普遍作用，其作用机制可能不是组织或器官特异性的，它可能为预防和治疗炎症性肺病等炎症性肺病的潜在临床应用提供有价值的线索。 ARDS。新型治疗剂在不同动物模型中的潜在保护作用的实验研究将有利于未来的药物转化和临床试验。