AC-NP改善大鼠低氧性肺动脉高压

AC-NP ameliorates pulmonary hypertension in rats

目的明确AC-NP(一种新型的钠尿肽分子)对于低氧性肺动脉高压的在体效应。方法采用间断性减压低氧的方法复制低氧性肺动脉高压(HPH)大鼠模型,以AC-NP〔50μg/(kg·d)〕治疗HPH大鼠1周。检测分析血流动力学指标,以及右心室和肺动脉的重构情况。结果低氧可致大鼠肺动脉压异常升高。AC-NP治疗1周显著降低HPH大鼠的肺动脉压、肺血管阻力、右心室肥厚和肺动脉的肌化,同时肺血流量显著增加。另外,静脉急性给予AC-NP可以显著改善HPH大鼠的血流动力学指标。结论 AC-NP对HPH具有一定的治疗作用。

AIM To investigate the in vivo effects of AC-NP on hypoxia-induced pulmonary hypertension （HPH）. AC-NP is a novel 28-amino acid chimeric peptide, which combines the 17-amino acid ring of C type natriuretic peptide （CNP） with 6-amino acid N-terminus and 5-amino acid C-terminus of atrial natriuretic peptide （ANP）. METHODS The HPH model was developed by subjecting rats to hypobaric hypoxia. HPH rats were then treated with either VNP （50 μg/kg per day, i.p.） or saline （0.5 ml, i.p.） every day for 7 days. Hemodynamic indices, right ventricular hypertrophy （RVH） and remodeling of the pulmonary arteries were evaluated. RESULTS Hypobaric hypoxia induced severe HPH compared with that in normoxic control group. Treatment of HPH rats with VNP for 1 week significantly reduced mean pulmonary arterial pressure, pulmonary vascular resistance, RVH and muscularization of the pulmonary arteries, although pulmonary blood flow was increased in this group. In addition, acute i.v. administration of AC-NP significantly ameliorated pulmonary haemodynamics in HPH rats. CONCLUSION SAC-NP has certain therapeutic effects against HPH.