Huang Zilu, Lin Bingchun, Han Dongshan, Wang Xuan, Zhong Junyan, Wagenaar Gerry T M, Yang Chuanzhong, Chen Xueyu
Department of Neonatology, Affiliated Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, China.
Faculty of Science, VU University Amsterdam, Amsterdam, Netherlands.
Front Pediatr. 2022 Aug 9;10:943054. doi: 10.3389/fped.2022.943054. eCollection 2022.
Previous studies suggest that platelets are involved in fetal and adult lung development, but their role in postnatal lung development especially after premature birth is elusive. There is an urgent need to scrutinize this topic because the incidence of bronchopulmonary dysplasia (BPD), a chronic lung disease after premature birth, remains high. We have previously shown impaired platelet biogenesis in infants and rats with BPD. In this study, we investigated the role of anti-CD41 antibody-induced platelet depletion during normal postnatal lung development and thrombopoietin (TPO)-induced platelet biogenesis in mice with experimental BPD. We demonstrate that platelet deficient mice develop a BPD-like phenotype, characterized by enlarged alveoli and vascular remodeling of the small pulmonary arteries, resulting in pulmonary arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). Vascular remodeling was potentially caused by endothelial dysfunction demonstrated by elevated von Willebrand factor (vWF) concentration in plasma and reduced vWF staining in lung tissue with platelet depletion. Furthermore, TPO-induced platelet biogenesis in mice with experimental BPD improved alveolar simplification and ameliorated vascular remodeling. These findings demonstrate that platelets are indispensable for normal postnatal lung development and attenuation of BPD, probably by maintaining endothelial function.
先前的研究表明，血小板参与胎儿和成人肺部发育，但其在出生后肺部发育尤其是早产之后的作用仍不清楚。迫切需要仔细研究这一课题，因为早产之后的慢性肺部疾病支气管肺发育不良（BPD）的发病率仍然很高。我们之前已表明，患BPD的婴儿和大鼠存在血小板生成受损的情况。在本研究中，我们调查了抗CD41抗体诱导的血小板耗竭在正常出生后肺部发育过程中的作用，以及血小板生成素（TPO）诱导的血小板生成在实验性BPD小鼠中的作用。我们证明，血小板缺陷小鼠会出现类似BPD的表型，其特征为肺泡增大和小肺动脉血管重塑，进而导致肺动脉高压（PAH）诱导的右心室肥厚（RVH）。血管重塑可能是由内皮功能障碍引起的，这表现为血浆中血管性血友病因子（vWF）浓度升高，以及血小板耗竭时肺组织中vWF染色减少。此外，TPO诱导的实验性BPD小鼠血小板生成改善了肺泡简化并减轻了血管重塑。这些发现表明，血小板对于出生后正常肺部发育和BPD的缓解必不可少，可能是通过维持内皮功能来实现的。
