高原环境中妊娠期母体缺氧对胎羊心肌组织影响的实验研究

The effects of different altitudes on fetal myocardial during gestational hypoxia:an experimental study

目的 观察高原环境中妊娠期母体绵羊不同程度的缺氧造成胎羊心肌组织及线粒体结构和功能的改变。方法 选取 24 只平原环境生长的妊娠期绵羊，随机分为平原对照组（LAC），轻度低氧暴露组（MHE）和重度低氧暴露组（SHE），应用人工实验舱，通过调整各项参数，精确模拟高原低氧的气候环境，制作不同程度缺氧的妊娠期动物模型。实验结束后，解剖胎羊，对胎羊及其重要内脏器官称重。获取各组胎羊心肌组织进行病理切片，用苏木素-伊红（HE）染色法、扫描电子显微镜及透射电子显微镜技术检测观察胎羊心肌组织和线粒体的病理改变情况。结果 和LAC组相比，MHE组和 SHE 组胎羊体重均明显降低（P〈0.05）；和 LAC 组或 MHE 组相比，SHE 组胎羊心脏绝对重量明显降低（P〈0.05），而心脏相对重量未见明显差异性改变（P〉0.05）。心肌组织样本HE 染色、扫描电子显微镜及透射电子显微镜显示，MHE 组、 SHE 组和 LAC 组相比，胎羊的心肌组织出现了不同程度的损伤，线粒体的数量、大小、形态结构及分布发生不同程度的异常，其中以 SHE 组心肌和线粒体异常和损伤最为显著。结论 高原缺氧环境能对胎儿心肌组织及线粒体造成损伤，同时随着海拔高度的升高，心肌及线粒体的损伤程度逐渐加重，提示在高原缺氧状态下，心肌损伤程度和线粒体数量、大小、形态和分布具有相关性。

Objective This study was to observe the changes of structure and function of the myocardial tissue and mitochondria in fetal sheep induced by different levels of high-altitude hypoxia during pregnancy. Methods Twenty four maternal sheep from low altitude were divided into three groups randomly： low altitude control group （LAC） （n=8）, mild hypoxia exposure group （MHE） （n=8） and severe hypoxia exposure group （SHE） （n=8）. By adjusting the parameters of artificial experimental cabin, we have developed three groups of models with different levels of high-altitude hypoxia. After the experiment, the fetal sheep and its own important internal organs were weighed. The general morphology of myocardial tissue was determined by hematoxylin-eosin （HE） staining; the ultra-structural changes in myocardial fiber and mitochondrion were observed with scanning electron microscopy and transmission electron microscopy. Results The fetal lambs of MHE and SHE group showed a significant reduction in fetal weight relative to LAC group at the same gestational age （133 ± 3 days）. In addition, absolute heart weight was decreased in the SHE group when compared with LAC group or MHE group. Compared with LAC group, HE staining, SEM and TEM showed that the myocardial tissue and the morphological structure and distribution of mitochondria in MHE and SHE groups had different levels of abnormality and injury, especially in SHE group. Conclusions This primary experimental results shows that the different degrees of hypoxia exposure developed by different altitudes have negative impact on the development of fetal sheep’s cardiovascular system, with the altitude increasing, the degree of myocardium and mitochondria injury increased, and the degree of myocardial injury was related to the quantity and morphology of mitochondria.