Hepatocyte growth factor intervention on rats with pulmonary hypertension and effect of endothelial cell membrane microparticles

Abstract

To explore the effect of transfection of adenovirus carrying hepatocyte growth factor (HGF) on pulmonary arterial hypertension (PAH) and endothelial cell membrane microparticles (EMP) in a rat model, and the underlying mechanism. Forty healthy male SD rats were randomly divided into four groups, the normal control group (NOR group), monocrotaline (MCT)-induced pulmonary hypertension group (PAH group), HGF treatment of PAH group (HGF group and THGF group) each with 10 rats. NOR group and the PAH Group: intratracheal instillation of 0.2 ml PBS solution; HGF group: intratracheal instillation of 0.2 ml HGF one times; THGF Group: intratracheal instillation of 0.2 ml HGF one times, and then 1 week repeat again. Different interventions after 2 weeks, the rats was measured mean pulmonary arterial pressure, right ventricular hypertrophy index calculation, HE staining index of pulmonary arterial wall thickness, area index, plasma levels of endothelial cell microparticles. HGF intratracheal instillation after 2 weeks, HGF and THGF groups of SD rats mPAP, RVHI, TI, AI decreased significantly compared with PAH group (P < 0.05). PAH group was increased in particulate levels at different time points significantly higher levels of horizontal (P < 0.05). The EMP levels in HGF group which at 7 and 14 days after dosing were significantly decreased compared with PAH.It still higher than the NOR group (P < 0.05). And after administration of 7 days, 14 days, the EMP level of HGF group was significantly lower than before administration (P < 0.05). Thought airway instillation transfected HGF, pulmonary artery pressure can reduce greater degree, but can't achieve complete reversal. It can inhibit the pulmonary artery wall thickening and maintain effective lumen area, delaying the right ventricular hypertrophy by reducing the membrane particles within the lung, thereby promoting endothelial cell repair to achieve the goal of intervention in pulmonary hypertension.