The roles of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor in the pathogenesis of hypoxia-induced pulmonary hypertension in neonatal rats / 中国新生儿科杂志

ABSTRACT

Objective To studytherolesof hypoxia-inducible factor-lalpha( HIF-1α )and vascular endothelial growth factor ( VEGF) in the pathogenesis of hypoxia-induced pulmonary hypertension ( HPH) in neonatal rats.Methods Wistar neonatal rats were assigned into HPH group and the control group using random number table method. Neonatal rats in HPH group were exposed to hypoxia according to HPH model. On day 3 , 7 ,14 and 210f hypoxia,the mean pulmonary artery pressure ( mPAP) , the level of mRNA and protein expression of HIF-1α and VEGF in lung tissue were examined using RT-PCR and Western blot methods respectively. The correlation of HIF-1,VEGF and mPAP were also analyzed. Results The mPAP ( mmHg)in HPH group on day 3 ,7 ,14 and 210f hypoxia were all higher than the control up[8.5±1.5)vs.5.2±1.0),(12.1±2.1)vs.9.6±0.8),(12.9±2.0)vs.(9.1±0.8),(21.0±2. 3) vs. (11. 2 + 1. 6) ,P < 0. 05]. 0n day 3, 7 and 140f hypoxia,the mRNA of HIF-1α in lung tissue of HPH group were significantly higher than the control group ( P <0. 05 ) . On day 70f hypoxia, the HIF-1αprotein in lung tissue of HPH group was significantly higher than the control group(P <0. 05 ) . On day 7 ,14 and 210f hypoxia,the mRNA and protein of VEGF in lung tissue of HPH group were also significantly higher than the control group( P <0. 05 ). Correlation analysis showed that HIF-1α protein were positively correlated with mPAP on day 3 ,7 . 14 and 210f hypoxia in HPH group ( r = 0. 504 .P = 0. 002) , and VEGF protein were positively correlated with mPAP in HPH group on day 7 , 14 and 210f hypoxia( r = 0. 782, P < 0. 001) .Conclusion Both HIF-1α and VEGF play roles in the occurrence and development of HPH in neonatal rats.