Association between expression of AMPK pathway and adiponectin, leptin, and vascular endothelial function in rats with coronary heart disease

摘要

OBJECTIVE: The aim of this study was to explore the association between the expression of adenosine monophosphate-activated protein kinase (AMPK) pathway and adiponectin (APN), leptin, and vascular endothelial function in rats with coronary heart disease (CHD). MATERIALS AND METHODS: Experimental rats were divided into three groups, including: control (Col) group, CHD model (CHD) group, and CHD+AMPK activator (CHD+AICAR) group. Except those in Col group, all rats were fed with high-fat diet and intraperitoneally injected with pituitrin to establish the CHD model. The levels of serum APN, leptin, and endothelin-1 (ET-1) were determined via enzyme-linked immunosorbent assay (ELISA). The content of serum nitric oxide (NO) was detected using the nitrate reductase method. Meanwhile, the expression of AMPK pathway-related protein AMPKα in vascular endothelial tissues was detected via Western blotting (WB). Aortic vascular endothelial cells (VECs) were cultured with AICAR or ET-1 in vitro. Subsequently, the expressions of AMPK pathway and protein kinase B (AKT) pathway-related proteins were determined through co-immunoprecipitation and WB. Moreover, the expression level of NO in VECs was determined using the DAF-FM DA fluorescence probe. RESULTS: Compared with Col group, CHD group showed significantly decreased levels of serum APN and NO (p0.05), significantly increased the levels of leptin and ET-1 (p0.05), as well as remarkably decreased protein expression of p-AMPKα in vascular endothelial tissues (p0.05). After injection of AMPK activator AICAR (200 mg/kg), the protein expression of p-AMPKα in CHD rats was significantly activated (p0.05). The levels of serum APN and NO were remarkably upregulated (p0.05), while the levels of leptin and ET-1 were significantly reduced (p0.05). Besides, AICAR could evidently activate the activity of AMPK pathway in VECs in vitro, upregulate the protein levels of p-eNOS (Ser1177) and p-AMPKα, and promote the secretion of NO (p0.05). In addition, AICAR remarkably inhibited ET-1-induced expression of AKT pathway (p0.05). CONCLUSIONS: Activating the AMPK pathway may play a positive role in the normal function of VECs and exert a certain curative effect on CHD in rats.