Effects of vascular endothelial growth factor inhibitor SU5416 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension
10.3760/cma.j.issn.2096-2932.2023.12.008
- VernacularTitle:血管内皮生长因子抑制剂SU5416对新生大鼠缺氧性肺动脉高压肺血管重塑的研究
- Author:
Tan WEI
1
;
Huimin FENG
;
Tong LI
;
Jing CAO
Author Information
1. 新疆医科大学儿科学院,乌鲁木齐 830054
- Keywords:
Hypoxic pulmonary hypertension;
Newborns;
Pulmonary vascular remodeling;
Vascular endothelial growth factor;
SU5416
- From:Chinese Journal of Neonatology
2023;38(12):745-750
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effects of vascular endothelial growth factor (VEGF) inhibitor SU5416 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).Methods:Thirty-two neonatal rats (age 7~10 d) were randomly assigned into normoxia group, hypoxia group, SU5416+hypoxia group and SU5416+normoxia group according to corresponding treatments. The endpoint was 14 d after treatments. Right ventricular systolic pressure (RVSP) was measured and cardiac and pulmonary tissue were sampled on the day. Right ventricular hypertrophy index (RVHI) was calculated. After HE staining, the morphological changes of pulmonary vessels were observed under light microscope.Media thickness (MT), external diameter(ED), cross-sectional area of tunica media (MA) and total cross-sectional area(TA) of pulmonary arterioles were measured. MT%(MT/ED) and MA%(MA/TA) were calculated as indicators of pulmonary vascular remodeling. The levels of VEGF and α-smooth muscle actin (α-SMA) in pulmonary vessels were examined using immunohistochemistry (IHC) method.Results:RVSP, RVHI, MT% and MA% in hypoxia group and SU5416+hypoxia group were significantly higher than normoxia group and SU5416+normoxia group ( P<0.05). These indicators in SU5416+hypoxia group were also higher than hypoxia group ( P<0.05),and no significant differences existed between SU5416+normoxia group and normoxia group ( P>0.05). The levels of α-SMA and VEGF in pulmonary vessels in SU5416+hypoxia group and hypoxia group were significantly higher than normoxia group and SU5416+normoxia group ( P<0.05), and α-SMA and VEGF in SU5416+hypoxia group higher than hypoxia group ( P<0.05). Conclusions:VEGF inhibitor SU5416 may exacerbate pulmonary hypertension and increase pulmonary vascular remodeling in neonatal HPH rats.