低氧对斑马鱼胚胎心脏和血管发育及相关基因表达的影响

研究以斑马鱼(Danio rerio)为研究模型,选择心脏和血管荧光标记的2个品系斑马鱼为实验材料,设定低氧和常氧2种水体溶氧条件,用荧光显微镜检测低氧胁迫对胚胎形态结构、心脏和血管外部形态、心率、胚胎躯干部主要血管形成的影响.研究发现低氧导致胚胎存活率低于常氧.低氧不仅滞后胚胎发育,而且造成胚胎形态异常.低氧胁迫后斑...

THE EFFECT OF HYPOXIA ON HEART AND VASCULAR MORPHOLOGICAL DEVELOPMENT AND RELATED GENES EXPRESSION IN ZEBRAFISH EMBRYOS

In this study, we used transgenic zebrafish (Danio rerio) with green fluorescence protein labeling in the heart and vasculature as study models. Two dissolved oxygen conditions, hypoxia and normoxia, were set. The morphological structure of the embryo, heart and vascular shape, heart rate, and formation of the main vessel in the embryonic trunk were measured and analyzed by fluorescence microscopy. We found that the survival rate of embryos under hypoxia was reduced. Hypoxia not only delayed embryonic development but also caused abnormal morphology. Heart malformations in zebrafish embryos exposed to hypoxia mainly manifested as pericardial effusion and developmental arrest in the linear heart tube stage. Although the heart tube could differentiate into the atrium and ventricle, the right cyclization process could not be completed. Vascular development in zebrafish embryos was also affected by hypoxia. Hypoxia narrowed the diameter of the embryonic dorsal aorta and posterior cardinal vein, shortened the distance between the posterior cardinal vein and the dorsal longitudinal anastomotic vessel, caused abnormal blood vessel growth in the interstitial cells of the embryo, and led to the specific disappearance of the parachordal vessels and a lack of subintestinal venous vessels. The study aimed to elucidate the mechanism by which hypoxia impacts cardiovascular development. In situ hybridization and qPCR were performed to test the changes in cardiovascular development-related genes localization and quantity and explore the mechanism of cardiovascular development under different conditions of dissolved oxygen. Based on the functions of these genes in cardiovascular development, we speculated that hypoxia likely impacts cardiac looping via the Tbx5 gene. In addition, abnormal cardiac development under hypoxia might be attributed to impair cardiac looping. Hypoxia could impact vessel development through the VEGF/VEGFR and Notch signaling pathways. In conclusion, hypoxia caused embryo development arrest, heart and vascular abnormalities, and expression changes in cardiovascular development-related genes. Whether hypoxic stress in the early embryo development stage would affect the morphological structures and physiological functions of adult zebrafish remains to be further studied.