Effect of beraprost sodium on HPH rats and expression of oxygen-sensitive Kv channels in pulmonary artery smooth muscle / 西安交通大学学报(医学版)

ABSTRACT

Objective To explore the effect of beraprost sodium (BPS) on hypoxia-induced pulmonary artery hypertension (HPH) in rats and the expression of oxygen-sensitive Kv channels in pulmonary artery smooth muscle (PASM).Methods The HPH model of rats was established by exposing rats to low-pressure and low-oxygen cabin which was auto-modulated for 8h every day.Rats in the BPS group were given an intragastric administration of BPS [300 μg/(kg · d)],while those in the control group and HPH group were given an intragastric administration of 3 ml/kg of 0.9％ saline.After 4 weeks,the mean pulmonary artery pressure (mPAP) was measured and right heart ventricle hypertrophy index (RVHI) was calculated;pulmonary artery remodeling was evaluated by HE staining;the expressions of Kv 1.2,Kv 1.5 and Kv2.1 in the pulmonary artery were detected by Real-time PCR and Western blot.Results The HPH model was successfully established in rats exposed to chronic hypoxia for 4 weeks.Compared with those in HPH group,mPAP,RVHI and pulmonary artery remodeling were decreased in BPS group [mPAP(13.48±2.18)mmHg vs.(23.87±2.23)mmHg vs.(17.09±1.20)mmHg;RVHI0.28±0.02 vs.0.46±0.03 vs.0.36±0.04;％ area of medial smooth muscle35.72±6.58 vs.68.52±5.64 vs.46.58±8.43;P＜0.05],and the mRNA and protein expressions of Kv 1.2,Kv 1.5 and Kv 2.1 were increased (relative protein expression levelKv1.2,0.78±0.10 vs.0.15±0.03 vs.0.57±0.13;Kv1.5,0.61±0.10 vs.0.31±0.05 vs.0.59±0.13;Kv2.1,0.29±0.05 vs.0.10±0.02 vs.0.28±0.07;P＜0.05).Conclusion BPS can improve pulmonary arterial hypertension induced by hypoxia,and upregulate the decreased mRNA and protein expressions of Kv 1.2,Kv 1.5 and Kv 2.1 in pulmonary artery.