Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
J Heart Lung Transplant. 2024 Mar;43(3):496-507. doi: 10.1016/j.healun.2023.10.009. Epub 2023 Oct 14.
Diseased animal models play an extremely important role in preclinical research. Lacking the corresponding animal models, many basic research studies cannot be carried out, and the conclusions obtained are incomplete or even incorrect. Right ventricular (RV) outflow tract (RVOT) obstruction leads to RV pressure overload (PO) and reduced pulmonary blood flow (RPF), which are 2 of the most important pathophysiological characteristics in pediatric cardiovascular diseases and seriously affect the survival rate and long-term quality of life of many children. Due to the lack of a neonatal mouse model for RVOT obstruction, it is largely unknown how RV PO and RPF regulate postnatal RV and pulmonary development. The aim of this study was to construct a neonatal RVOT obstruction mouse model.
Here, we first introduced a neonatal mouse model of RVOT obstruction by pulmonary artery banding (PAB) on postnatal day 1. PAB induced neonatal RVOT obstruction, RV PO, and RPF. Neonatal RV PO induced cardiomyocyte proliferation, and neonatal RPF induced pulmonary dysplasia, the 2 features that are not observed in adult RVOT obstruction. As a result, PAB neonates exhibited overall developmental dysplasia, a sign similar to that of children with RVOT obstruction.
Because many pediatric cardiovascular diseases are associated with RV PO and RPF, the introduction of a neonatal mouse model of RVOT obstruction may greatly enhance our understanding of these diseases and eventually improve or save the lives of many children.
患病动物模型在临床前研究中起着极其重要的作用。缺乏相应的动物模型，许多基础研究无法进行，得出的结论不完整甚至不正确。右心室（RV）流出道（RVOT）梗阻导致 RV 压力超负荷（PO）和肺血流量（RPF）减少，这是儿科心血管疾病最重要的 2 种病理生理特征，严重影响许多儿童的生存率和长期生活质量。由于缺乏 RVOT 梗阻的新生小鼠模型，RV PO 和 RPF 如何调节出生后 RV 和肺发育在很大程度上仍不清楚。本研究旨在构建一种新生 RVOT 梗阻的小鼠模型。
在这里，我们首次通过在出生后第 1 天进行肺动脉环扎术（PAB）引入了一种新生 RVOT 梗阻的小鼠模型。PAB 导致新生 RVOT 梗阻、RV PO 和 RPF。新生 RV PO 诱导心肌细胞增殖，而新生 RPF 诱导肺发育不良，这是成年 RVOT 梗阻中观察不到的 2 个特征。因此，PAB 新生鼠表现出整体发育不良，这一迹象类似于 RVOT 梗阻患儿。
由于许多儿科心血管疾病与 RV PO 和 RPF 有关，引入新生 RVOT 梗阻的小鼠模型可能会极大地增强我们对这些疾病的理解，最终改善或挽救许多儿童的生命。
