Gaseous signalling molecule SO2 via HippoMST pathway to improve myocardial fibrosis of diabetic rats.
Mol Med Rep
; 16(6): 8953-8963, 2017 Dec.
Article
en En
| MEDLINE
| ID: mdl-28990064
ABSTRACT
Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the HippoMST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male SpragueDawley rats were randomly divided into four groups (10 rats per group) Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with LAspartic acid ßhydroxamate (HDX) group (HDX group). Diabetic rats models were established by intraperitoneal injection of STZ (40 mg/kg) Following model establishment, intraperitoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the HippoMST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosisassociated protein Bcell lymphoma associated protein X, caspase3 and caspase9 were upregulated, and Bcl2 expression was downregulated. The expression of ERS and HippoMST pathwayassociated proteins, including CHOP, GRP94, MST1 and MST2, were significantly upregulated. By contrast, these abovementioned changes were reversed by SO2 treatment. Compared with STZ group, the HDX group had a further increase of myocardial fibrosis and apoptosis, while there were no statistically significant differences in the expression of Bax/Bcl2, caspase3, caspase9 and ERS and HippoMST pathwayassociated proteins. The results of the present study demonstrated that the gaseous signal molecule SO2 can effectively improve the myocardial fibrosis of diabetic rats, and its mechanism may be associated with reduced apoptosis and ERS by downregulated HippoMST pathway.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dióxido de Azufre
/
Transducción de Señal
/
Proteínas Serina-Treonina Quinasas
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Quinasas Quinasa Quinasa PAM
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Miocardio
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2017
Tipo del documento:
Article