Experimental Study On The Role That Hepatocyte Growth Factor Plays In The Onset Of Pulmonary Hypertension In A Rat Model.

Objective: ⑴.To establish a practical rat model with pulmonary arterialhypertension (PAH) that has similar underlying etiologies to the clinical cases;⑵.To study the role that HGF plays in the onset of PAH and its possiblemechanisms. Methods: Animal model of SD rat with PAH was establishedthrough left pneumonectomy plus monocrotaline (MCT) injection. At days 7, 14,21 and 28 after MCT injection, experimental rats were measured of theirhemodynamics and then killed, with their remaining right lungs and heartsharvested for histological and molecular analyses, to identify the pulmonaryvascular remodeling and to find out the changes of the target cytokines. Results:Compared with the normal controls, manifestations of severe right heart failure,well-elevated pulmonary arterial pressure and serious right heart hypertrophywere observed in the pulmonary hypertensive rats 28 days after left lungresection and MCT injection. Pulmonary vascular remodeling, with exhibitionsof pulmonary fibrosis, hyperplasia of pulmonary arterial endothelial cells andvascular smooth muscle cells in tunica media, as well as decease of vasculardensity were also observed according to the pathological findings. In comparisonto the normal controls, intra-pulmonary HGF and eNOS expression underwent anobvious decrease in a time-dependent manner at both mRNA and protein levels 4weeks after MCT injection, which exhibited a close correlation with pulmonaryvascular remodeling( ). On the contrary, ET-1 and TGF-βwere obviousup-regulated in the pulmonary hypertensive rats'lung, which are thought to becritically involved in PAH-linked fibrogenic events. Finally, c-met /HGF receptoralmost stayed unchanged at both levels. Conclusion: ⑴. Rat model with PAHestablished through left pneumonectomy and MCT is a practical andconfirmative one with good imitation to the clinical cases in underlyingetiologies, so as to be used for further study on PAH. ⑵. Down-regulation ofintra-pulmonary HGF expression, which is thought to result from up-regulationof TGF-β, may be the keypoint that probably leads to PAH in our animal model.In addition, decrease of eNOS expression and thus NO production while increaseof ET-1 may be the main reason for elevated pulmonary arterial pressure.