Zhang Xiyang, Nickerson Rhea, Burton Lauren, Stueck Ashley, Holbein Bruce, Cheng Zhenyu, Zhou Juan, Lehmann Christian
Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Biomedicines. 2024 Jun 29;12(7):1452. doi: 10.3390/biomedicines12071452.
Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator DIBI in murine lung infection induced by intratracheal (strain PA14) administration. DIBI is a polymer with a polyvinylpyrrolidone backbone containing nine 3-hydroxy-1-(methacrylamidoethyl)-2-methyl-4(1H) pyridinone (MAHMP) residues per molecule and was given by intraperitoneal injection either as a single dose (80 mg/kg) immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24 h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by , via its anti-bacterial and anti-inflammatory effects.
铁在肺部感染中起着关键作用，这不仅是因为它在炎症免疫反应中的功能，还因为它是细菌生长的一个重要因素。铁螯合是一种潜在的治疗方法，可抑制细菌生长和病理性增加的促炎介质产生。本研究旨在探讨铁螯合剂二异丁酰亚胺（DIBI）对气管内注射（PA14菌株）诱导的小鼠肺部感染的影响。DIBI是一种具有聚乙烯吡咯烷酮主链的聚合物，每个分子含有九个3-羟基-1-（甲基丙烯酰胺基乙基）-2-甲基-4（1H）吡啶酮（MAHMP）残基，通过腹腔注射给药，要么在PA14给药后立即给予单剂量（80mg/kg），要么给予双剂量（PA14给药后4小时给予第二剂量）。结果显示，PA14给药24小时后，肺组织和支气管肺泡灌洗液（BALF）中的肺NF-κBp65水平以及各种炎症细胞因子（TNFα、IL-1β、IL-6）水平均显著升高。单剂量DIBI对肺部或BALF中的细菌载量或炎症反应没有影响。然而，两剂量的DIBI显著降低了细菌载量，减弱了NF-κBp65的上调，减少了炎症细胞因子的产生，并减轻了肺组织损伤。我们的研究结果支持这样的结论，即铁螯合剂DIBI可以通过其抗菌和抗炎作用减轻由[具体细菌名称未给出]诱导的肺损伤。
