妊娠期缺氧对胎儿心血管发育的影响及相关机制的研究

Congenital heart disease is a congenitaldeformities，which is caused by genetic combined with environmental factors. Its morbidity is increasing year by year in Xinjiang.In the country, most Epidemiological analysisand related research indicates that the occurrence of congenital heart disease is in close touch with body gestational hypoxia. However, the Pathological and physiological effects and mechanism of the body gestational hypoxia on fetal heart developmentis unknown. This project is targeted at researching the abnormal fetal cardiovascular development with the exposure of hypoxia environment in duration of pregnancy. We observe the development of fetal sheep cardiovascular system when exposed under certain density or time span of hypoxia environment by using echocardiography, pathological, proteomics methods.The incidence and progression of congenital heart disease of the subjects had been analized comprehensively at the level of gross anatomy, protein structure . Both qualative and quantitive relation between hypoxia and congenital heart disease had been subsequently observed. This revealed the effect that enviromental factor made to the mechanism of incidence of the disease.The result of this research has significant effect on enhancing primary prevention, minimizing birth defect and the mechanism with it.

先天性心脏病是由遗传因素和环境因素共同作用导致的先天性畸形，其在新疆地区的发病率逐年上升。国内外已有多项流行病学统计分析及相关研究间接显示先天性心脏病的发生与母体妊娠期缺氧有一定联系，但其对胎儿心脏发育的确切病理生理影响及相关机制尚不明确。本研究拟以绵羊为研究对象，在母体孕期分别给予不同程度的低氧环境暴露，通过超声心动图检测、细胞及组织病理学检测、蛋白质组学检测等方法，对低氧暴露条件下胎儿心血管系统发育的解剖结构、病理水平、蛋白水平进行实时、动态、系列的观察检测，探索母体妊娠期缺氧与胎儿心脏发育异常之间的联系及量效关系，揭示母体妊娠期低氧的环境因素对疾病发病机制的影响，为先天性心脏病一级预防、诊断和治疗提供重要的理论依据。

先天性心脏损伤是由遗传因素和环境因素共同作用导致的先天性畸形，其在新疆地区的发病率逐年上升。本研究以妊娠期绵羊为研究对象，在母体孕期分别给予不同程度的低氧环境暴露，通过超声心动图检测、细胞及组织病理学检测、蛋白质组学等方法，对低氧暴露条件下胎儿心血管系统发育的解剖结构、病理水平、蛋白水平进行实时、动态、系列的观察及精确检测。结果显示建模后实验组与对照组比较，妊娠期绵羊呼吸频率减低，心率升高，运动、饮食减少，蛋白质氧化损伤的生物标志物羰基和细胞氧化损伤的生物标志物丙二醛水平升高，虽然超声检查未发现各组动物关键的心血管结构畸形存在，但HE染色及扫描电镜检测显示实验组动物的心脏组织出现了不同程度的细胞组织水肿且线粒体分布异常，蛋白检测共鉴定了16676个肽段和2506个蛋白质，共鉴定出80个差异表达的蛋白，其中41个蛋白表达上调，39个蛋白表达下调。实验成功应用西北人工实验舱成功建立了不同程度的妊娠期绵羊高原缺氧模型，可操作性强，且证实高原低氧环境引起了妊娠期绵羊的氧化应激损伤，进一步证实了在高原环境下，母体妊娠期缺氧能够干扰胚胎的心血管系统生长发育，导致出生后心脏组织病理学及蛋白组学结果发生异常。