Cao Jing, Luo Jia-Yuan, Wu Dian, Zhao Qian, Li Ming-Xia
Department of Neonatology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2021 Jan;23(1):103-110. doi: 10.7499/j.issn.1008-8830.2009005.
To study the role of vascular endothelial growth factor-A (VEGF-A) in pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH) by regulating survivin (SVV).
A total of 96 neonatal rats were randomly divided into three groups: HPH+VEGF-A group, HPH group, and control group. Each group was further randomly divided into 3-, 7-, 10-, and 14-day subgroups (=8 in each subgroup). The neonatal rats in the HPH+VEGF-A and HPH groups were intratracheally transfected with adenoviral vectors with or without VEGF-A gene respectively. Those in the control group were given intratracheal injection of normal saline and were then fed under normoxic conditions. The direct measurement method was used to measure mean right ventricular systolic pressure (RVSP). Hematoxylin-eosin staining was used to observe the morphological changes of pulmonary vessels under a light microscope and calculate the percentage of media wall thickness (MT%) and the percentage of media wall cross-sectional area (MA%) in the pulmonary arterioles. Immunohistochemistry was used to measure the expression levels of VEGF-A and SVV in lung tissue.
The HPH group had a significantly higher mean RVSP than the control and HPH+VEGF-A groups at each time point ( < 0.05). Pulmonary vascular remodeling occurred in the HPH group on day 7 of hypoxia, while it occurred in the HPH+VEGF-A group on day 10 of hypoxia. On day 7 of hypoxia, the HPH group had significantly higher MT% and MA% than the control and HPH+VEGF-A groups ( < 0.05). On days 10 and 14 of hypoxia, the HPH and HPH+VEGF-A groups had significantly higher MT% and MA% than the control group ( < 0.05). The HPH and HPH+VEGF-A groups had significantly higher expression of VEGF-A than the control group at each time point ( < 0.05). On days 3 and 7 of hypoxia, the HPH+VEGF-A group had significantly higher expression of VEGF-A than the HPH group ( < 0.05). On day 14 of hypoxia, the HPH group had significantly higher expression of SVV than the control group ( < 0.05). The HPH+VEGF-A group had significantly higher expression of SVV than the control group at each time point ( < 0.05). On days 3 and 7 of hypoxia, the HPH+VEGF-A group had significantly higher expression of SVV than the HPH group ( < 0.05).
Prophylactic intratracheal administration of exogenous VEGF-A in neonatal rats with HPH can inhibit pulmonary vascular remodeling and reduce pulmonary arterial pressure by upregulating the expression of SVV in the early stage of hypoxia. This provides a basis for the interventional treatment of pulmonary vascular remodeling in neonatal HPH.
通过调节生存素（SVV）研究血管内皮生长因子 -A（VEGF-A）在新生大鼠缺氧性肺动脉高压（HPH）肺血管重塑中的作用。
将96只新生大鼠随机分为三组：HPH+VEGF-A组、HPH组和对照组。每组再随机分为3天、7天、10天和14天亚组（每组8只）。HPH+VEGF-A组和HPH组的新生大鼠分别经气管内转染含或不含VEGF-A基因的腺病毒载体。对照组经气管内注射生理盐水，然后在常氧条件下饲养。采用直接测量法测量平均右心室收缩压（RVSP）。苏木精 - 伊红染色用于在光学显微镜下观察肺血管的形态变化，并计算肺小动脉中膜壁厚百分比（MT%）和中膜壁横截面积百分比（MA%）。免疫组织化学用于测量肺组织中VEGF-A和SVV的表达水平。
在每个时间点，HPH组的平均RVSP均显著高于对照组和HPH+VEGF-A组（<0.05）。缺氧第7天HPH组发生肺血管重塑，而缺氧第10天HPH+VEGF-A组发生肺血管重塑。缺氧第7天，HPH组的MT%和MA%显著高于对照组和HPH+VEGF-A组（<0.05）。缺氧第10天和14天，HPH组和HPH+VEGF-A组的MT%和MA%显著高于对照组（<0.05）。在每个时间点，HPH组和HPH+VEGF-A组的VEGF-A表达均显著高于对照组（<0.05）。缺氧第3天和7天，HPH+VEGF-A组的VEGF-A表达显著高于HPH组（<0.05）。缺氧第14天，HPH组的SVV表达显著高于对照组（<0.05）。在每个时间点，HPH+VEGF-A组的SVV表达均显著高于对照组（<0.05）。缺氧第3天和7天,HPH+VEGF-A组的SVV表达显著高于HPH组（<0.）。
对患有HPH的新生大鼠预防性气管内给予外源性VEGF-A可通过上调缺氧早期SVV的表达来抑制肺血管重塑并降低肺动脉压。这为新生HPH肺血管重塑的介入治疗提供了依据。
