Acute lung injury (ALI) is an inflammatory lung disease. miRNA-92a (miR92a) is induced in the lungs of ALI patients and mediates inflammatory reactions. In this study, a RP1-linked R3V6 (RP1R3V6) peptide was synthesized and evaluated as a carrier of anti-microRNA-92a oligonucleotide (AMO92a) into the lungs of an ALI animal model. In addition to the carrier function, the RP1-linked peptide can have anti-inflammatory effects in the lungs, since RP1 is an antagonist of the receptors for advanced glycation end-products (RAGEs). In a gel retardation assay, the RP1R3V6 peptide formed a spherical complex with AMO92a. In an in vitro delivery assay to L2 rat lung epithelial cells, RP1R3V6 had a lower AMO92a delivery efficiency than R3V6 and polyethyleneimine (PEI25k; 25 kDa). However, RP1R3V6 had an additional anti-inflammatory effect, reducing tumor necrosis factor-α (TNF-α) in lipopolysaccharide-activatedmacrophage cells. With the combined effects of AMO92a and RP1, the RP1R3V6/AMO92a complex reduced the miR92a level more efficiently than did the R3V6/AMO92a and PEI25k/AMO92a complexes. The RP1R3V6/AMO92a complex was administered into the lungs of ALI animals by intratracheal instillation. As a result, the expression of phosphatase and tensin homolog, a target of miR92a, was increased in the lungs. Furthermore, the RP1R3V6/AMO92a complex decreased the TNF-α and interleukin-1β (IL-1β) levels more efficiently than did the PEI25k/AMO92a and R3V6/AMO92a complexes, decreasing the damage in the lungs. These results suggest that RP1R3V6 is a useful carrier of AMO92a and has anti-inflammatory effects in an ALI animal model.

中文翻译：

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使用 RP1 连接肽递送 miRNA-92a 抑制剂在急性肺损伤模型中引发抗炎作用。

急性肺损伤（ALI）是一种炎症性肺病。miRNA-92a (miR92a) 在 ALI 患者的肺中被诱导并介导炎症反应。在这项研究中，合成了一种 RP1 连接的 R3V6 (RP1R3V6) 肽，并作为抗 microRNA-92a 寡核苷酸 (AMO92a) 的载体在 ALI 动物模型的肺部进行了评估。除了载体功能外，RP1 连接的肽还可以在肺部产生抗炎作用，因为 RP1 是晚期糖基化终末产物 (RAGE) 受体的拮抗剂。在凝胶阻滞试验中，RP1R3V6 肽与 AMO92a 形成球形复合物。在体外在 L2 大鼠肺上皮细胞的递送试验中，RP1R3V6 的 AMO92a 递送效率低于 R3V6 和聚乙烯亚胺 (PEI25k; 25 kDa)。然而，RP1R3V6 具有额外的抗炎作用，可减少脂多糖激活的巨噬细胞中的肿瘤坏死因子-α (TNF - α )。在 AMO92a 和 RP1 的联合作用下，RP1R3V6/AMO92a 复合物比 R3V6/AMO92a 和 PEI25k/AMO92a 复合物更有效地降低了 miR92a 水平。通过气管内滴注将 RP1R3V6/AMO92a 复合物施用于 ALI 动物的肺部。结果，磷酸酶和张力蛋白同源物（miR92a 的靶标）在肺中的表达增加。此外，RP1R3V6/AMO92a 复合物降低了 TNF - α和白细胞介素-1β (IL-1 β ) 水平比 PEI25k/AMO92a 和 R3V6/AMO92a 复合物更有效，从而减少了肺损伤。这些结果表明 RP1R3V6 是 AMO92a 的有用载体，并且在 ALI 动物模型中具有抗炎作用。