Department of Medical Imaging and Radiation Sciences, Monash University, Victoria, Clayton, Australia.
Department of Anatomy and Developmental Biology and the Biomedicine Discovery Institute, Monash University, Victoria, Clayton, Australia.
Exp Physiol. 2020 Aug;105(8):1256-1267. doi: 10.1113/EP088117. Epub 2020 Jun 12.
What is the central question of this study? What is the immediate impact of moderate preterm birth on the structure and function of major conduit arteries using a pre-clinical sheep model? What is the main finding and its importance? Postnatal changes in conduit arteries, including a significant decrease in collagen within the thoracic aortic wall (predominately males), narrowed carotid arteries, reduced aortic systolic blood flow, and upregulation of the mRNA expression of cell adhesion and inflammatory markers at 2 days of age in preterm lambs compared to controls, may increase the risk of cardiovascular impairment in later life.
The aim of this work was to compare the structure and function of the conduit arteries of moderately preterm and term-born lambs and to determine whether vascular injury-associated genes were upregulated. Time-mated ewes were induced to deliver either preterm (132 ± 1 days of gestation; n = 11 females and n = 10 males) or at term (147 ± 1 days of gestation; n = 10 females and n = 5 males). Two days after birth, ultrasound imaging of the proximal ascending aorta, main, right and left pulmonary arteries, and right and left common carotid arteries was conducted in anaesthetized lambs. Lambs were then killed and segments of the thoracic aorta and left common carotid artery were either snap frozen for real-time PCR analyses or immersion-fixed for histological quantification of collagen, smooth muscle and elastin within the medial layer. Overall there were few differences in vascular structure between moderately preterm and term lambs. However, there was a significant decrease in the proportion of collagen within the thoracic aortic wall (predominantly in males), narrowing of the common carotid arteries and a reduction in peak aortic systolic blood flow in preterm lambs. In addition, there was increased mRNA expression of the cell adhesion marker P-selectin in the thoracic aortic wall and the pro-inflammatory marker IL-1β in the left common carotid artery in preterm lambs, suggestive of postnatal vascular injury. Early postnatal differences in the function and structure of conduit arteries and evidence of vascular injury in moderately preterm offspring may place them at greater risk of cardiovascular impairment later in life.
本研究的核心问题是什么？使用临床前绵羊模型，中度早产对主要输送动脉的结构和功能有何直接影响？主要发现及其重要性是什么？与对照组相比，早产羔羊在出生后 2 天，输送动脉发生了变化，包括胸主动脉壁内胶原显著减少（主要是雄性）、颈动脉变窄、主动脉收缩血流减少以及血管细胞黏附及炎症标志物的 mRNA 表达上调，这可能增加其在生命后期发生心血管损伤的风险。
本研究旨在比较中度早产和足月产羔羊的输送动脉结构和功能，并确定血管损伤相关基因是否上调。对同期妊娠的母羊进行诱导分娩，分别分娩中度早产（妊娠 132±1 天；n=11 只雌性和 n=10 只雄性）或足月（妊娠 147±1 天；n=10 只雌性和 n=5 只雄性）羔羊。在麻醉的羔羊中进行近端升主动脉、主、右和左肺动脉以及右和左颈总动脉的超声成像。然后杀死羔羊，并对胸主动脉和左颈总动脉的部分组织进行实时 PCR 分析，或进行浸泡固定以对中层胶原、平滑肌和弹力蛋白进行组织学定量。总体而言，中度早产和足月羔羊的血管结构差异较小。然而，在早产羔羊中，胸主动脉壁内胶原的比例显著降低（主要是雄性）、颈总动脉变窄以及主动脉收缩血流峰值降低。此外，在早产羔羊的胸主动脉壁中细胞黏附标志物 P 选择素和左颈总动脉中的促炎标志物白细胞介素-1β的 mRNA 表达增加，提示产后血管损伤。中度早产后代出生后输送动脉功能和结构的早期差异以及血管损伤的证据可能使他们在生命后期更易发生心血管损伤。
