Sen'kova A V, Savin I A, Chernolovskaya E L, Davydova A S, Meschaninova M I, Bishani A, Vorobyeva M A, Zenkova M A
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russian Federation.
Acta Naturae. 2024 Apr-Jun;16(2):61-71. doi: 10.32607/actanaturae.27393.
Acute lung injury (ALI) is a specific form of lung inflammation characterized by diffuse alveolar damage, noncardiogenic pulmonary edema, as well as a pulmonary and systemic inflammation. The pathogenesis of ALI involves a cascade inflammatory response accompanied by an increase in the local and systemic levels of proinflammatory cytokines and chemokines. The development of molecular tools targeting key components of cytokine signaling appears to be a promising approach in ALI treatment. The development of lipopolysaccharide (LPS)-induced ALI, as well as the feasibility of suppressing it by an aptamer targeting the proinflammatory cytokine TNF-α, was studied in a mouse model. The TNF-α level was shown to increase significantly and remain steadily high during the development of ALI. LPS-induced morphological signs of inflammation in the respiratory system become most pronounced 24 h after induction. Intranasal administration of TNF-α-targeting aptamers conjugated with polyethylene glycol (PEG-aptTNF-α) to mice with ALI reduced the intensity of inflammatory changes in lung tissue. Assessment of the levels of potential TNF-α target genes (, , and ) showed that their expression levels in the lungs increase during ALI development, while declining after the application of PEG-aptTNF-α. Therefore, topical use of TNF-α- targeting aptamers may be an efficient tool for treating ALI and other inflammatory lung diseases.
急性肺损伤（ALI）是一种以弥漫性肺泡损伤、非心源性肺水肿以及肺部和全身炎症为特征的特定形式的肺部炎症。ALI的发病机制涉及级联炎症反应，同时局部和全身促炎细胞因子及趋化因子水平升高。开发针对细胞因子信号关键成分的分子工具似乎是治疗ALI的一种有前景的方法。在小鼠模型中研究了脂多糖（LPS）诱导的ALI的发生发展以及通过靶向促炎细胞因子TNF-α的适体抑制其发生发展的可行性。结果显示，在ALI发展过程中，TNF-α水平显著升高并持续保持在较高水平。LPS诱导的呼吸系统炎症形态学体征在诱导后24小时最为明显。给ALI小鼠经鼻内给予与聚乙二醇偶联的靶向TNF-α的适体（PEG-aptTNF-α）可降低肺组织炎症变化的强度。对潜在的TNF-α靶基因（ 、 和 ）水平的评估表明，它们在肺中的表达水平在ALI发展过程中升高，而在应用PEG-aptTNF-α后下降。因此，局部使用靶向TNF-α的适体可能是治疗ALI和其他炎症性肺部疾病的有效工具。
