基于microRNA水平研究孕前移居高原对子代先天性心脏病的影响

High altitude environment causes fetal long-term chronic hypoxia, and fetal intrauterine hypoxia is a very important cause of congenital heart disease. Effects of microRNA on pregnancy at high altitude area of filial generation with CHD have not yet been reported in the literature. The project analysis microRNA expression profiles and selected differentially microRNAs using RT-PCR validation of microarray results by replication of pregnant rats at high altitude model, collection moved to plateau of childbearing of congenital heart disease in children cases, and study clinical significance and value of the property on microRNA to identify congenital heart disease as molecular markers and evaluate the microRNA prospects for congenital heart disease screening, and further elucidate the pathogenesis of congenital heart disease to provide reliable experimental evidence., Eugenics and painless, effective advanced treatment means provide by this project for the plateau area development.

高原环境导致胎儿长期慢性缺氧,而胎儿宫内缺氧又是先天性心脏病的一个十分重要的诱因。microRNA对于孕前移居高原地区子代的CHD患儿的影响目前尚未有相关文献报道。本项目通过复制孕鼠高原移居模型，收集移居高原孕妇生育的先天性心脏病患儿病例，进行microRNA表达谱分析，然后对选定的差异microRNA使用RT-PCR进行芯片结果的验证。探讨microRNA作为鉴别先天性心脏病的分子标志物的价值和临床意义,评估microRNA用于先天性心脏病筛查的前景,并且为进一步阐明先天性心脏病的发病机制提供可靠的实验依据。为高原地区的开发、发展提供优生优育和无痛、有效的先进诊疗手段。

高原环境导致胎儿长期慢性缺氧，而胎儿宫内缺氧又是先天性心脏病的一个十分重要诱因。microRNA对于孕前移居高原地区子代CHD患儿的影响目前尚未有相关文献报道。本项目通过复制孕鼠高原移居模型，收集移居高原孕妇生育的先天性心脏病患儿病例，进行microRNA表达谱分析，然后对选定的差异microRNA使用RT-PCR进行芯片结果的验证。结果发现共同差异表达microRNAs有:miR-26a-5p，miR-30a-5p，miR-107，miR-425-5p，miR-28-3p。应用RT-PCR方法进行验证，结果表明：先心病患者血标本与高原正常组相比上调的miR有：miR-26a-5p，miR-30a-5p，miR-107，miR-425-5p；下调的miR有：miR-28-3p。与平原对照组比较，高原缺氧组大鼠血液miR-425-5p，miR-107，miR-30a-5p，miR-26a-5p水平明显上调，miR-28-3p水平明显下调，与高原缺氧组比较红景天组miR-107，miR-30a-5p，miR-26a-5p明显下调，西洋参组miR-30a-5p水平明显下调，miR-28-3p水平明显上调，吸氧组miR-425-5p，miR-107，miR-30a-5p，miR-26a-5p水平明显下调，miR-28-3p水平明显上调。与平原对照组比较，高原缺氧组大鼠心脏miR-425-5p，miR-107，miR-30a-5p，miR-26a-5p水平明显上调，miR-28-3p水平明显下调，与高原缺氧组比较红景天组miR-425-5p，miR-107，miR-30a-5p水平明显下调，miR-28-3p水平明显上调；西洋参组miR-425-5p，miR-107，miR-30a-5p，miR-26a-5p水平改变没有显著性差异，miR-28-3p水平明显上调。miR-28-3p的靶基因FAS蛋白表达与平原对照组比较，高原缺氧组明显上调，与高原缺氧组比较，红景天组FAS蛋白表达明显下调，miR-28-3p可能通过调控FAS基因表达影响高原缺氧先心病的进展。以上结果提示miR-28-3p可以作为筛选先天性心脏病早期诊断的生物标志物。