Establishment of a rat model with pulmonary arterial hypertension and its functioning mechanism / 中华胸心血管外科杂志

ABSTRACT

Objective To study the alteration of hepatocyte growth factor and c-met in the lungs of rats with pulmonary arterial hypertension and its possible underlying mechanisms.Methods Left pneumonectomy plus monocrotaline injection was used for rat PAH model.Rats were executed after measurement of their pulmonary arterial pressure at 1,2, 3 and 4 weeks after MCT injection.Then the right lung and heart were harvested for further analyses.Expression of HGF and c-met was determined by RT-PCR and Western blot.Expression of eNOS and caspase-3 was analyzed immunohistochemically and intrapulmonary TGF-β and ET-1 was analyzed with ELISA.Results Compared with the normal controls, manifestations of right heart hypertrophy and failure, well-elevated pulmonary arterial pressure were observed 28 days after left lung resection and MCT injection.Pulmonary vascular remodeling (i.e., pulmonary fibrosis, hyperplasia of pulmonary arterial endothelial cells and vascular smooth muscle cells in tunica media, as well as decease of vascular density) was observed.Intrapulmonary HGF expression decreased in a time-dependent manner at both mRNA and protein levels 4 weeks after MCT injection, while c-met stayed unchanged.Immunohistochemically, expression of eNOS was reduced and caspase-3 strengthened.On the contrary, ET-1 and TGF-β were obviously up-regulated(P ＜ 0.01).Conclusion Intrapulmonary HGF expression was obviously downregulated in PAH rats, accompanying with reduction of NO and increase of ET-1 and TGF-β expression, while c-met still unchanged.