| Objective: To investigate the protein and m RNA expression levels of platelet-derived growth factor-BB(PDGF-BB),extracellular regulated kinase(ERK),hypoxia-inducible factor-1α(HIF-1α),and proliferating cell nuclear antigen(PCNA)in lung tissues of neonatal rats with hypoxic pulmonary hypertension(HPH)and their relationship with right ventricular systolic pressure(RVSP),right ventricular hypertrophy index(RVHI),and pulmonary vascular remodeling.index(RVHI)and pulmonary vascular remodeling,and to investigate the effects of PDGF-BB on the expression levels of ERK,HIF-1α and PCNA and their mechanistic roles in pulmonary vascular remodeling in HPH neonatal rats.Methods: 128 Wistar neonatal rats were randomly divided into PDGF-BB+HPH group,HPH group,PDGF-BB+normal oxygen group and normoxia group(n=32).On the next day,the HPH model was established in the PDGF-BB+HPH group and HPH group,and the PDGF-BB+normal oxygen group and normoxic group were kept under normoxia.The RVSP,RVHI were measured at 3d,7d,14 d and 21 d.The transfection of PDGF-BB adenovirus was observed under fluorescence microscope,the morphology of small pulmonary arteries was observed under light microscope and vascular remodeling indexes were calculated.The expression of PDGF-BB,ERK,HIF-1α,PCNA and m RAN expression level of lung tissue were detected by immunohistochemistry and RT-PCR.Results:(1)RVSP: Compared with the normoxia group,the RVSP of neonatal rats in the HPH group was higher than that in the normoxia group at all time points,suggesting that the modeling of neonatal rats in HPH was successful,and the RVSP of neonatal rats in the PDGF-BB+HPH group was higher than that in the HPH group at 3d,7d and 14 d of modeling(P<0.05),and the PDGF-BB+ normoxia group was higher than that in the normoxia group(P < 0.05).(2)Immunofluorescence: green fluorescence was visible at 3d and 7d after adenovirus transfection in the PDGF-BB+HPH group,indicating that adenovirus successfully transfected lung tissue.(3)RVHI:compared with the normoxia group,the RVHI of neonatal rats in the PDGF-BB+HPH group was higher than that in the normoxia group at all observation points(P<0.05),and there was no difference between the RVHI of neonatal rats in the HPH and PDGF-BB+normoxia groups at 3d of modeling(P>0.05),and at 7d and 14 d of modeling,the RVHI of neonatal rats in the HPH group was higher than that in the normoxia group(P<0.05).RVHI of neonatal rats was higher than that of PDGF-BB + normoxia group and normoxia group(P<0.05),and PDGF-BB + HPH group was higher than that of HPH group(P<0.05),and PDGF-BB + normoxia group was higher than that of normoxia group(P<0.05),suggesting that exogenous increase of PDGF-BB and early hypoxia could aggravate right ventricular hypertrophy in HPH neonatal rats;4)pulmonary vascular Remodeling:vascular remodeling appeared in PDGF-BB+HPH group at 3d of modeling,and started to appear in HPH group at 7d.At 3d of modeling,MA%and MT%in PDGF-BB+HPH group were higher than those in HPH group,PDGF-BB+normal oxygen group and normoxia group(P<0.05),and at 7d,14 d and 21 d of modeling,MA%,MT%in PDGF-BB+HPH group and HPH group were higher than those in PDGF-BB+HPH group.MT%were higher in the PDGF-BB+HPH and HPH groups than in the PDGF-BB+ normoxia and normoxia groups(P<0.05);5)Expression of PDGF-BB,ERK,HIF-1α,PCNA and m RNA in lung tissues: the protein expression of PDGF-BB,ERK,HIF-1α,PCNA and m RNA expression in the PDGF-BB+HPH and HPH groups increased at each time point compared with the normoxia group.The expression levels of PDGF-BB,ERK,HIF-1α,PCNA and m RAN increased in the PDGF-BB+HPH group compared with the normoxic group at 3d,7d and 14 d.The PDGF-BB+HPH group showed enhanced expression compared with the HPH group(P<0.05),and the PDGF-BB+ normoxic group was higher than the normoxic group(P<0.05).There was no significant difference between the HPH group and the PDGF-BB+HPH group(P > 0.05).Conclusion: Through PDGF-BB overexpression,it may activate ERK/HIF-1α signaling pathway,promote the proliferation of PASMCs,upregulate the expression of PCNA,promote pulmonary vascular remodeling,increase pulmonary artery pressure,and cause right ventricular hypertrophy,if blocking PDGF-BB may become a new target for neonatal HPH treatment. |
PDF Full Text Request