Mechanism of salidroside preventing myocardial fibrosis based on TLR4-mediated pyroptosis pathway / 中国药房
China Pharmacy
; (12): 1053-1059, 2023.
Artículo
en Chino
| WPRIM (Pacífico Occidental)
| ID: wpr-972946
Biblioteca responsable:
WPRO
ABSTRACT
OBJECTIVE To investigate the effects of salidroside (Sal) on myocardial fibrosis and pyroptosis and its potential mechanism. METHODS The mice were randomly divided into control group, model group and Sal low-dose, medium-dose and high-dose groups, with 10 mice in each group. Except for the control group, the mice in other groups were injected subcutaneously with isoproterenol 5 mg/(kg·d)to prepare the myocardial fibrosis model. Since modeling, mice in the Sal low-dose, medium-dose and high-dose groups were given 10, 30 and 50 mg/kg of Sal by intragastric administration every day; control group and model group were given 10 mL/kg of normal saline by intragastric administration every day, for 14 consecutive days. After the last medication, the mice were sacrificed; hematoxylin-eosin staining was used to observe pathological change of myocardial tissue and calculate the diameter of myocardial cell; Masson and Sirius Red staining were used to observe the degree of myocardial fibrosis in mice and calculate the collagen volume fraction (CVF); quantitative real-time PCR was performed to detect the mRNA expressions of collagen type Ⅰ (Col Ⅰ), α-smooth muscle actin (α-SMA), Toll-like receptor 4 (TLR4), NOD-like receptor pyrin domain containing 3 (NLRP3), caspase-1 andgasdermin D (GSDMD) in myocardial tissues. The total protein expressions of Col Ⅰ, α-SMA, TLR4, NLRP3,caspase-1 and GSDMD in myocardial tissues and protein-positive cell score were measured by Western blot assay and immunohistochemistry. RESULTS Compared with control group, the myocardial cells in the model group were enlarged, the arrangement of myocardial fibers was disordered, the matrix metabolism was significantly increased, the CVF in myocardial tissue was significantly increased, and the mRNA and protein expression levels of Col Ⅰ, α-SMA, TLR4, NLRP3, caspase-1 and GSDMD were elevated and protein-positive cell score was increased significantly (P<0.01). Compared with model group, the myocardial cell morphology was clearer, myocardial fibrosis was alleviated, and the levels of the above indicators in myocardial tissue of Sal medium-dose and high-dose groups had been reversed to varying degrees, especially in Sal high-dose group(P<0.05 or P<0.01). In addition, the Sal low-dose group also reversed some fibrosis and pyroptosis-related indicators to some extent. CONCLUSIONS Sal can significantly prevent the occurrence and development of myocardial fibrosis, and the mechanism of action may be related to the inhibition of TLR4-mediated pyroptosis pathway in myocardial tissue.
Texto completo:
Disponible
Base de datos:
WPRIM (Pacífico Occidental)
Idioma:
Chino
Revista:
China Pharmacy
Año:
2023
Tipo del documento:
Artículo