RESUMO
Pulmonary arterial hypertension (PAH) is an insidious and progressive disease that is triggered by various cardiopulmonary diseases. Inflammation has an important role in the progression of PAH. Osthole (Ost) is a coumarin that has clear antiinflammatory properties. The present study aimed to investigate the effects of Ost on PAH, and to explore the mechanism underlying this effect. Using the monocrotaline (MCT)induced PAH rat model, the effects of Ost on PAH were investigated. Rats were subcutaneously administered a single dose of MCT (50 mg/kg) to establish the PAH model, followed by daily treatment with Ost (10 or 20 mg/kg) by gavage for 28 days. The mean pulmonary arterial pressure (mPAP) was measured and histological analysis was performed. The results demonstrated that Ost significantly decreased mPAP, and reduced thickening of the pulmonary artery, compared with in rats in the MCT group. To further determine whether the effects of Ost on MCTinduced PAH were associated with inflammatory responses, the nuclear factorκB (NFκB) p65 signaling pathway was investigated by western blot analysis. The results demonstrated that Ost increased inhibition of the NFκB p65 signaling pathway. In conclusion, the results of the present study demonstrate that Ost may suppress the progression of MCTinduced PAH in rats, which may be, at least partially, mediated through modulation of the NFκB p65 signaling pathway.
Assuntos
Anti-Inflamatórios/uso terapêutico , Cumarínicos/uso terapêutico , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Monocrotalina , Artéria Pulmonar/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , NF-kappa B/análise , Tamanho do Órgão/efeitos dos fármacos , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Ratos Sprague-DawleyRESUMO
A prior study demonstrated that icariin (ICA) could repress angiotensin II-induced apoptosis in H9c2 cells. The activation of mitochondrial apoptotic pathways may play a crucial role in this phenomenon. In this study, we explored the potential protective roles of ICA in apoptosis in cardiomyocytes, cardiac remodelling, and the underlying mechanisms with regard to the mitochondrial apoptotic pathway in rats with spontaneous hypertension. The oral administration of ICA (20 and 40mg/kg/d) inhibited cardiomyocyte apoptosis and ameliorated left heart ventricle remodelling and abnormal mitochondria. ICA also decreased the blood pressure of model rats. ICA treatment increased the expression of Bcl-2 and decreased the expression of p53, Bax, Bok and cleaved caspase 3 in model rats, which suggests the potential mechanism underlying this effect. In summary, ICA inhibits the apoptosis of cardiomyocytes and ameliorates cardiac remodelling. The potential mechanism may relate to the inhibition of the mitochondrial apoptotic pathway.