Abstract
BackgroundThe present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway.MethodsA total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR.ResultsThe results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05).ConclusionsART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.
Highlights
The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/Nuclear transcription factor (NF-κB) signaling pathway
Model establishment and grouping A total of 40 6-week-old Sprague-Dawley rats were randomly divided into five groups as follows: Healthy group (n = 8), diabetes mellitus group (DM group; n = 8), diabetes mellitus treated with a low dose of ART group (DM + ART 50 mg/kg group; n = 8), diabetes mellitus treated with a high dose of ART group (DM + ART 100 mg/kg group; n = 8) and diabetes mellitus treated with insulin group (DM + INS 6 U/kg group; n = 8)
Compared with the rats in the Type Diabetes Mellitus (DM) group, the heart and body weight were increased in kg), diabetes mellitus treated with a high concentration of ART; DM + INS, diabetes mellitus treated with insulin the DM + ART (50 mg/kg), DM + ART (100 mg/kg) and reduced compared with those in the DM + ART
Summary
The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway. The combination of AGEs and RAGE induces the production of reactive oxygen species, followed by activation of major cellular signal transduction pathways, such as the NF-κB signaling pathway, resulting in the regulation of a variety of inflammatory and profibrotic factors, such as CD68 and matrix metalloproteinases (MMPs), which cause vascular endothelial damage, cardiomyocyte edema degeneration, myocardial fibrosis and other pathological changes, and are involved in the development of diabetes-induced cardiovascular complications [17,18,19,20]. The role of the RAGE/NF-κB-mediated signaling pathway in cardiovascular pathology was further explored by constructing a rat model of type 1 diabetes
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