Inhibitory effects of formononetin on the monocrotalineinduced pulmonary arterial hypertension in rats.
Mol Med Rep
; 21(3): 1192-1200, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-31922224
ABSTRACT
Pulmonary arterial hypertension (PAH) is a fatal syndrome resulting from enhanced pulmonary arterial pressure and pulmonary vessel resistance. Perivascular inflammation and extracellular matrix deposition are considered to be the crucial pathophysiologic bases of PAH. Formononetin (FMN), a natural phytoestrogen isolated from red clover (Trifolium pratense), has a variety of proapoptotic, antiinflammatory and antitumor activities. However, the therapeutic effectiveness of FMN for PAH remains unclear. In the present study, 60 mg/kg monocrotaline (MCT) was first used to induce PAH in rats, and then all rats were treated with different concentrations of FMN (10, 30 and 60 mg/kg/day). At the end of this study, the hemodynamics and pulmonary vascular morphology of rats were evaluated. Specifically, matrix metalloproteinase (MMP)2, transforming growth factor ß1 (TGFß1) and MMP9 were measured using western blot and immunohistochemical staining. Collagen type I, collagen type III, fibronectin, monocyte chemotactic protein1, tumor necrosis factorα, interleukin1ß, ERK and NFκB were quantified using western blotting. The results demonstrated that FMN significantly alleviated the changes of hemodynamics and pulmonary vascular morphology, and decreased the MCTinduced upregulations of TGFß1, MMP2 and MMP9 expression levels. Meanwhile, the expression levels of collagen type I, collagen type III and fibronectin in rat lungs decreased after FMN treatment. Furthermore, the phosphorylated ERK and NFκB also decreased after FMN treatment. Taken together, the present study indicated that FMN serves a therapeutic role in the MCTinduced PAH in rats via suppressing pulmonary vascular remodeling, which may be partially related to ERK and NFκB signals.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Monocrotalina
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Sistema de Señalización de MAP Quinasas
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Hipertensión Arterial Pulmonar
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Hemodinámica
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Isoflavonas
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2020
Tipo del documento:
Article