| Summary: | 碩士 === 國防醫學院 === 生理學研究所 === 102 === Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary resistance, abnormal vascular remodeling in pulmonary arteries (PAs), and right ventricular (RV) hypertrophy. Magnolol extracted from Chinese herb has an antioxidant and anti-inflammatory activity, and an inhibitory effect in endothelial cell proliferation. The aim of this study was to investigate whether magnolol alleviates the symptoms of pneumonectomy and monocrotaline ( PE + MCT ) - induced PAH in rats. The PAH model was established in rats injected with monocrotaline (60 mg/kg) at 7 day after pneumonectomy, and the rats randomly received a vehicle or various doses of magnolol intraperitoneally from Day 6 to Day 35 after pneumonectomy. The histological assay and related molecular studies were preformed. Magnolol significantly decreases pulmonary arterial pressure from 70 mmHg down to 30 mmHg. Treatment with magnolol of PAH rats reduced the RV weight / left ventricular (LV) + septum weight ratio accompanied by decreased pulmonary vascular medial thickness in PAH rats. In addition, the increased protein expression of ET-1、ETAR、Akt、Erk、Ang II and ACE、AT-1 and GSK3-catenin observed in rats with PAH was markedly attenuated by magnolol. We also explored the lungs ACE2, AT2R protein expression, in recent years many papers confirmed PAH occurs when increased ACE2 and AT2R reaction conditions can be improved. The mechanisms involved may be associated with down-regulation of ET-1 and Ang II-related processes. For ACE2, AT2R protein expression, but also by magnolol increase its protein expression. In conclusion, magnolol exerts a beneficial effect in PE + MCT induced PAH through inhibition of GSK 3 beta/beta-catenin in the mechanism and would increase the ACE2, AT2R protein expression, improve PAH.
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