NOX2/ROS通路调控猪胎盘血管生成的作用机制研究

仔猪初生重直接影响其生长发育和成活率，而胎盘血管生成异常是导致仔猪初生重低的重要原因。迄今对同窝胎猪不同胎盘间血管生成差异的调节机制尚不清楚。申请人前期研究发现，初生重低的仔猪其胎盘血管密度显著降低、血管生成标记物（CD31和VEGF）表达量显著下调；同时发现NADPH氧化酶亚型2（NOX2）/活性氧（ROS）通路被激活。据此申请人提出如下科学假设：NOX2/ROS是胎盘血管生成的负调控通路。本项目拟在前期基础上，以猪血管内皮细胞为模型，采用NOX2表达调控和药物阻断策略，研究NOX2在血管生成中的作用及机制；然后以不同营养状况的母猪为对象，采用NOX2天然抑制剂和ROS清除剂，研究NOX2/ROS通路对胎盘血管生成和仔猪初生重的影响。研究结果不仅可揭示NOX2/ROS通路调控猪胎盘血管生成的作用机制，同时也为研发促进胎盘血管发育、提高仔猪初生重的营养策略提供理论依据。

The birth weight of piglets significantly affects survival and postnatal growth of newborn piglets. Placental angiogenesis abnormality is the major cause of low birth weight (LBW) of piglets. However, the mechanism of the differences in placental angiogenesis among the litter remains unclear. Our previous study demonstrated that the density of placental vessels was diminished in LBW piglets, and the expression levels of placental angiogenic markers (CD31 and VEGF) were noticeably decreased, as well as NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS) pathway was activated in the LBW piglets. Thus, we propose that NOX2/ROS is a negative regulation pathway of placental angiogenesis. On the basis of previous study, firstly, we would investigate the role and mechanism of NOX2 in placental angiogenesis on pig iliac endothelium cell lines by agonists, inhibitors and gene editing method. Secondly, we would examine the effect of inhibition NOX2-derived ROS on placental angiogenesis and birth weight of piglets through dietary supplementation NOX2 inhibitor and ROS scavenger in the sows during gestation. This study could not only reveal the mechanism of NADPH oxidase 2-derived ROS in the regulation of angiogenesis in porcine placenta, but also provide theoretical basis in the nutritional strategy to improve placental angiogenesis and birth weight of piglets.