Li Debao, Qiu Lisheng, Hong Haifa, Chen Hao, Zhao Peibin, Xiao Yingying, Zhang Hao, Sun Qi, Ye Lincai
Department of Thoracic and Cardiovascular Surgery, School of Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, China.
Department of Thoracic and Cardiovascular Surgery, School of Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Cell Biosci. 2023 Jun 19;13(1):112. doi: 10.1186/s13578-023-01058-8.
Pulmonary vein stenosis (PVS), one of the most challenging clinical problems in congenital heart disease, leads to secondary pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy. Due to the lack of a rodent model, the mechanisms underlying PVS and its associated secondary effects are largely unknown, and treatments are minimally successful. This study developed a neonatal rat PVS model with the aim of increasing our understanding of the mechanisms and developing possible treatments for PVS.
PVS was created at postnatal day 1 (P1) by banding pulmonary veins that receive blood from the right anterior and mid lobes. The condition was confirmed using echocardiography, computed tomography (CT), gross anatomic examination, hematoxylin and eosin (H&E) staining, fibrosis staining, and immunofluorescence. Lung and RV remodeling under the condition of PVS were evaluated using H&E staining, fibrosis staining, and immunofluorescence.
At P21, echocardiography revealed a change in wave form and a decrease in pulmonary artery acceleration time-indicators of PAH-at the transpulmonary valve site in the PVS group. CT at P21 showed a decrease in pulmonary vein diameter in the PVS group. At P30 in the PVS group, gross anatomic examination showed pulmonary congestion, H&E staining showed wall thickening and lumen narrowing in the upstream pulmonary veins, and immunofluorescence showed an increase in the smooth muscle layers in the upstream pulmonary veins. In addition, at P30 in the PVS group, lung remodeling was evidenced by hyperemia, thickening of pulmonary small vessel walls and smooth muscle layers, and reduction of the number of alveoli. RV remodeling was evidenced by an increase in RV free wall thickness.
A neonatal rat model of PVS was successfully established, showing secondary lung and RV remodeling. This model may serve as a useful platform for understanding the mechanisms and treatments for PVS.
肺静脉狭窄（PVS）是先天性心脏病中最具挑战性的临床问题之一，可导致继发性肺动脉高压（PAH）和右心室（RV）肥厚。由于缺乏啮齿动物模型，PVS及其相关继发效应的潜在机制在很大程度上尚不清楚，治疗效果也微乎其微。本研究建立了新生大鼠PVS模型，旨在加深我们对其机制的理解，并开发PVS的可能治疗方法。
在出生后第1天（P1）通过结扎接受来自右前叶和中叶血液的肺静脉来制造PVS。使用超声心动图、计算机断层扫描（CT）、大体解剖检查、苏木精和伊红（H&E）染色、纤维化染色和免疫荧光来确认病情。使用H&E染色、纤维化染色和免疫荧光评估PVS条件下的肺和RV重塑。
在P21时，超声心动图显示PVS组经肺动脉瓣部位的波形改变以及肺动脉加速时间（PAH指标）降低。P21时的CT显示PVS组肺静脉直径减小。在PVS组的P30时，大体解剖检查显示肺充血，H&E染色显示上游肺静脉壁增厚和管腔狭窄，免疫荧光显示上游肺静脉平滑肌层增加。此外，在PVS组的P30时，肺重塑表现为充血、肺小血管壁和平滑肌层增厚以及肺泡数量减少。RV重塑表现为RV游离壁厚度增加。
成功建立了新生大鼠PVS模型，显示出继发性肺和RV重塑。该模型可作为理解PVS机制和治疗方法的有用平台。
