PDF(Pubmed)
Abstract：
Intrauterine growth restriction (IUGR) with rapid postnatal catch-up growth is strongly associated with pulmonary vascular dysfunction in adulthood, whereas IUGR with delayed growth in early postnatal life results in long-term brain deficits. In the present study, it was hypothesized that IUGR with early moderate catch-up growth may alleviate pulmonary vascular remodeling in adulthood without affecting memory function. An IUGR model was established by restricting maternal nutrition during pregnancy. Different growth patterns were achieved by adjusting the litter size in each group during lactation. Rats meeting the weight requirement at weaning were selected for subsequent studies at three time points (3, 9 and 13 weeks). Cognitive function was evaluated using a Y-maze. Invasive hemodynamic measurements were conducted to measure the mean pulmonary arterial pressure (mPAP). In addition, primary pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (PVECs) were cultured to investigate their role in the increase in mPAP following rapid catch-up growth. The results showed that memory function deficits in the rats in the delayed growth group were associated with reduced proliferation of neural stem cells in the subgranular zone of the hippocampus. Furthermore, moderate catch-up growth at the three time points improved memory function while maintaining a normal mPAP. In adult IUGR rats experiencing rapid catch-up growth, although memory function improved, elevated mPAP and medial thickening of pulmonary arterioles were observed. Additionally, PASMCs exhibited excessive proliferation, migration and anti-apoptotic activity in the rapid catch-up group, and PVECs also displayed excessive proliferation. These results suggested that moderate catch-up growth after IUGR is a better strategy for optimal cognition and cardiovascular health in adulthood compared with rapid catch-up growth or delayed growth.
摘要：
宫内生长受限（IUGR）与产后快速追赶生长与成年期的肺血管功能障碍密切相关。而出生后早期生长延迟的IUGR会导致长期的脑损伤。在本研究中,据推测,早期中度追赶性生长的IUGR可缓解成年期肺血管重塑,而不影响记忆功能.通过限制孕妇在怀孕期间的营养来建立IUGR模型。通过调整泌乳期间每组的产仔数来实现不同的生长模式。在三个时间点(3、9和13周)选择满足断奶时体重要求的大鼠用于后续研究。使用Y迷宫评估认知功能。进行有创血流动力学测量以测量平均肺动脉压（mPAP）。此外,培养原代肺动脉平滑肌细胞（PASMC）和肺血管内皮细胞（PVEC），以研究它们在快速追赶生长后mPAP增加中的作用。结果表明，延迟生长组大鼠的记忆功能缺陷与海马颗粒下区域神经干细胞增殖减少有关。此外，在三个时间点的适度追赶增长改善了记忆功能，同时保持了正常的mPAP。在经历快速追赶生长的成年IUGR大鼠中，虽然记忆功能有所改善，观察到mPAP升高和肺小动脉内侧增厚。此外,PASMC表现出过度增殖，在快速追赶组中的迁移和抗凋亡活性，PVECs也表现出过度增殖。这些结果表明，与快速追赶增长或延迟增长相比，IUGR后的适度追赶增长是成年期最佳认知和心血管健康的更好策略。
