产前超声联合磁共振、lncRNAs评估母体氧疗干预先心病胎儿神经系统发育障碍的研究

Ours previous projiect has reported the high risks of neurodevelopmental abnormalities in fetuses with congenital heart defect (CHD). These abnormalities are associated with cerebral ischemia and hypoxia due to abnormal cardiac circuits and/or function. Our resent studies demonstrated that maternal hyperoxygenation (MH) improved cardiac transport function through enlarging heart chamber dimensions and increasing myocardium deformation in fetuses with certain type of CHD. Studies on annimal and human showed that MH can increase the oxygen content of fetal brain. Theoretically, MH may improve cerebral development and reduce brain injury by enhancing the cerebral oxygenation and nutrition supplies in CHD fetuses with neurodevelopmental abnormalities. As so far, there has not been a systematic evaluation of the effects of MH on cerebral development in fetus with CHD. This study is expected to systematically assess the change of fetal brain structure, volume, blood perfusion, cerebral oxygenation and metabolism in CHD fetus with abnormal neurodevelopment during MH using multiple imaging techniques (three-dimensional ultrasound, blood-oxygen-level-dependent MRI, proton magnetic resonance spectroscopy) and specific lnc RNAs. The purposes of the study are 1）to prove the improvement of neurodevelopment in fetus with CHD during/after MH; 2)to demonstrate MH indications and potential side-effects, searching for indivial therpay procedure.

我们前课题显示先心病胎儿伴发高风险神经系统发育障碍，这与心脏血流动力改变/心功能受损所致脑组织缺血缺氧有关。我们最近研究显示母体氧疗（MH）能增强先心病胎儿心脏运输氧/营养能力，动物和人体实验也表明MH能增加胎儿脑组织氧含量，所以理论上MH可改善脑循环氧/营养供给，促进神经系统发育。但国内外尚无MH干预先心病胎儿神经系统发育障碍的详细研究和系统评估。本研究旨在应用产前超声（三维容积、三维能量技术）联合磁共振（BOLD-MRI、1HMRS）、lncRNAs评估MH对高危先心病胎儿脑结构、容积、血流灌注、氧含量和代谢功能的影响，证明MH能够干预先心病胎儿神经系统发育障碍，探讨MH适应症和可能副作用。

本研究应用产前超声（三维容积、三维能量技术）联合磁共振、lncRNAs评估MH对高危先心病胎儿脑结构、容积、血流灌注、氧含量和代谢功能的影响，发现MH不同程度地改善先心病胎儿脑血流动力学、脑组织灌注，促进先心病胎儿脑容积生长追赶速度，可逆性提高先心病胎儿脑组织氧含量，提高脐血PO2和SO2水平，显著降低脐血中HIFs和Apaf-1浓度，降低脐血和脑组织lncRNAs的差异表达。这些改变与先心病类型相关，左心结构发育不良组更明显，完全性大动脉转位组次之，右心结构发育不良组无明显效应。而且氧疗效果会因先心病类型、神经系统基础发育状态、孕周、氧疗浓度和时间不尽相同。随访过程中没有发现可识别的母胎副作用。. 该研究显示对合并神经系统发育障碍的先心病胎儿，MH能够干预部分先心病胎儿神经系统发育障碍，减少脑损伤，改善预后, 减轻了家庭负担与社会负担，具有较大的间接经济效益；根据MH反应进行有的放矢的终止妊娠或及早治疗减缓病程，为产前咨询、围产期管理提供新的数据和方案，具有较大的社会效益。本研究已经发表论文6篇，其中SCI 5篇（Q1 4篇，Q2 1篇），中华期刊论文1篇；获湖南省科技进步奖三等奖两项（2019-02、2022-07）；获湖南医学科技奖二等奖一项(2021-02)；培养硕士研究生5名。