近年研究表明孕期宫内胎儿糖皮质激素（GCs）暴露在胎源性心血管病“早期编程”中起重要作用。文献和我们前期研究均显示：孕期GCs暴露的胎儿出生后血压升高、血管功能障碍，但其病理机制目前尚未阐明。我们动物预实验发现：不论孕期GCs暴露的胎儿还是成年子代，其血管中血管紧张素II受体（AT1R）表达均显著增加。据此我们提出假设：AT1R异常表达是孕期GCs暴露导致子代血管功能障碍“程序化”发生的一个关键因素。本课题将围绕AT1R，拟从分子、细胞、组织、动物水平及临床样本等多层次明确AT1R在血管功能障碍“程序化”发生中的作用；揭示产前GCs应用对胎儿血管AT1R表达的影响；阐明AT1R表达异常的调控机制和印迹效应；探讨AT1R阻滞剂对孕期GCs暴露高血压子代的降压效果。研究成果不仅为胎源性心血管疾病的早期防治提供基础理论指导，也为临床干预产前GCs应用的负面效应提供新思路。

Glucocorticoids (GCs) exposure during pregnancy play a critical role in “early life programming” of cardiovascular diseases in fetal origins. Published papers and our preliminary experimental results show that increased blood pressure and vascular dysfunction in the offspring exposed to prenatal GCs, but its “programmed” pathological mechanism remains uncertain. We further found that the expression of AT1R is significantly increased in the blood vessels, regardless of the prenatal GCs exposed the fetus or the adult offspring. To this end, we propose the hypothesis: the“programmed” pathogenesis of vascular dysfunction induced by prenatal GCs exposure is associated with abnormal expression of AT1R. This project will clarify the role of AT1R in the "programmed" occurrence of vascular dysfunction, reveal the effect of prenatal GCs application on vascular AT1R expression, elucidate the regulation mechanism and imprinting effect of AT1R abnormal expression, and investigate whether the AT1R inhibitor has better antihypertensive effect on prenatal GCs exposed adult offspring from multi-aspect of molecular, cellular, tissue, animal level and clinical samples. The data gained will provide new insight for the early prevention and treatment of hypertension in developmental origins, and also provide views for clinical intervention on negative effect of in prenatal GCs application.