Department of Neonatology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China.
Department of Radiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China.
BMC Pulm Med. 2023 Jun 15;23(1):209. doi: 10.1186/s12890-023-02498-1.
This study aimed to determine whether postnatal treatment with recombinant human IGF-1 (rhIGF-1)/binding peptide 3 (BP3) ameliorates lung injury and prevents pulmonary hypertension (PH) in bronchopulmonary dysplasia (BPD) models.
We used two models of BPD in this study: one model that was associated with chorioamnionitis (CA), stimulated by intra-amniotic fluid and exposure to lipopolysaccharide (LPS), whereas the other was exposed to postnatal hyperoxia. Newborn rats were treated with rhIGF-1/BP3 (0.2 mg/Kg/d) or saline via intraperitoneal injection. The study endpoints included the wet/dry weight (W/D) ratio of lung tissues, radial alveolar counts (RACs), vessel density, right ventricular hypertrophy (RVH), lung resistance, and lung compliance. Hematoxylin and eosin (H&E) and Masson staining were used to evaluate the degree of lung injury and pulmonary fibrosis. IGF-1 and eNOS expression were detected using western blotting or quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The levels of SP-C, E-cadherin, N-cadherin, FSP1, and Vimentin in the lung tissues were detected by immunofluorescence.
LPS and hyperoxia treatment increased lung injury and pulmonary fibrosis, enhanced RVH and total respiratory resistance, and decreased RAC, pulmonary vascular density and pulmonary compliance in young mice (all p < 0.01). Simultaneously, LPS and hyperoxia induced an increase in epithelial-mesenchymal transition (EMT) in airway epithelial cells. However, rhIGF-1/BP3 treatment reduced lung injury and pulmonary fibrosis, decreased RVH and total respiratory resistance, and enhanced RAC, pulmonary vascular density and pulmonary compliance, as well as inhibited EMT in airway epithelial cells in LPS and hyperoxia treated mice.
Postnatal rhIGF-1/BP3 treatment relieved the effects of LPS or hyperoxia on lung injury and prevented RVH, providing a promising strategy for the treatment of BPD.
本研究旨在确定产后给予重组人生长因子 1（rhIGF-1）/结合肽 3（BP3）治疗是否能改善肺损伤并预防支气管肺发育不良（BPD）模型中的肺动脉高压（PH）。
本研究使用了两种 BPD 模型：一种与绒毛膜羊膜炎（CA）相关，通过羊膜内注射液体和脂多糖（LPS）刺激，另一种则暴露于产后高氧环境中。新生大鼠通过腹腔注射接受 rhIGF-1/BP3（0.2mg/Kg/d）或生理盐水治疗。研究终点包括肺组织的湿/干重（W/D）比、肺泡计数（RAC）、血管密度、右心室肥厚（RVH）、肺阻力和肺顺应性。苏木精和伊红（H&E）和 Masson 染色用于评估肺损伤和肺纤维化的程度。使用 Western blot 或定量逆转录聚合酶链反应（qRT-PCR）检测 IGF-1 和 eNOS 的表达。通过免疫荧光检测肺组织中 SP-C、E-钙粘蛋白、N-钙粘蛋白、FSP1 和波形蛋白的水平。
LPS 和高氧处理增加了幼鼠的肺损伤和肺纤维化，增强了 RVH 和总呼吸阻力，降低了 RAC、肺血管密度和肺顺应性（均 p<0.01）。同时，LPS 和高氧诱导气道上皮细胞上皮-间充质转化（EMT）增加。然而，rhIGF-1/BP3 治疗减少了 LPS 和高氧处理小鼠的肺损伤和肺纤维化，降低了 RVH 和总呼吸阻力，增强了 RAC、肺血管密度和肺顺应性，并抑制了气道上皮细胞中的 EMT。
产后 rhIGF-1/BP3 治疗减轻了 LPS 或高氧对肺损伤的影响，并预防了 RVH，为治疗 BPD 提供了一种有前途的策略。
