Objectives: To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).
Methods: A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB genevia the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue.
Results: The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05).
Conclusions: Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure.
目的: 探讨血小板源性生长因子-BB（platelet-derived growth factor-BB，PDGF-BB）对缺氧性肺动脉高压（hypoxia pulmonary hypertension，HPH）新生大鼠肺血管重塑的影响。方法: 128只新生大鼠随机分为：PDGF-BB+HPH组、HPH组、PDGF-BB+常氧组、常氧组（各组n=32）。PDGF-BB+HPH组、PDGF-BB+常氧组经尾静脉注射13 μL 6×1010 PFU/mL携带PDGF-BB基因的腺病毒载体。转染腺病毒载体24 h后，HPH组和PDGF-BB+HPH组建立HPH新生大鼠模型。缺氧3、7、14、21 d检测右心室收缩压（right ventricular systolic pressure，RVSP），苏木精-伊红染色后光学显微镜下观察肺血管形态学变化及血管重塑指标（MA%、MT%），免疫组化法检测肺组织中PDGF-BB、增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）的表达水平。结果: PDGF-BB+HPH组和HPH组RVSP在各时间点均高于同日龄常氧组（P<0.05）。PDGF-BB+HPH组缺氧3 d出现血管重塑，HPH组缺氧7 d开始出现血管重塑；缺氧3 d时，PDGF-BB+HPH组MA%、MT%高于HPH组、PDGF-BB+常氧组、常氧组（P<0.05）；缺氧7、14、21 d时，PDGF-BB+HPH组和HPH组MA%、MT%均高于PDGF-BB+常氧组、常氧组（P<0.05）。PDGF-BB+HPH组、HPH组在各时间点PDGF-BB、PCNA表达均高于常氧组（P<0.05），缺氧3、7、14 d时，PDGF-BB+HPH组PDGF-BB、PCNA表达高于HPH组（P<0.05），PDGF-BB+常氧组PDGF-BB、PCNA表达较常氧组高（P<0.05）。结论: 外源性给予HPH新生大鼠PDGF-BB，可上调PCNA表达，促进肺血管重塑，提高肺动脉压力。.
Keywords: Neonatal rat; Platelet-derived growth factor-BB; Proliferation; Pulmonary hypertension; Vascular remodeling.