RESUMO
BACKGROUND Diabetes is a risk factor for coronary atherosclerosis and coronary heart disease. Resveratrol (RESV) is a natural compound with anti-inflammatory effects. The objective of this study is to evaluate the cardio protective effects of RESV in a diabetic rat model with coronary heart disease. MATERIAL AND METHODS Diabetic rat model with coronary heart disease was constructed by feeding high-fat and high-calorie diet, followed by injection of streptozotocin. The diabetic rats received RESV or DMSO as treatment. Insulin, total cholesterol, and total triglyceride levels in serum were measured using enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RESV in alleviating diabetic symptoms. Inflammatory factors, including tumor necrotic factor α, interleukin-6, interleukin-8, intracellular adhesion molecule 1, vascular-cell adhesion molecule 1, and monocyte chemoattractant protein-1 were assayed using ELISA. Real-time polymerase chain reaction and western blot analysis were performed to evaluate the impact of RESV treatment on the TLR4/MyD88/NF-κB signaling pathway (toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway). Hematoxylin and eosin staining was used to document pathological changes in cardiovascular muscles. RESULTS RESV preserved pancreatic tissue, which therefore reduced levels of glucose and triglycerides glyceride in serum. Inflammatory factors were also suppressed by RESV. TLR4/MyD88/NF-κB signaling pathway was downregulated after RESV treatment. CONCLUSIONS RESV offers protective effects of cardiovascular tissues in the diabetic rat model with coronary heart disease. Those effects are mediated by downregulating the TLR4/MyD88/NF-κB signaling pathway.
Assuntos
Doença das Coronárias/tratamento farmacológico , Resveratrol/farmacologia , Animais , Western Blotting , China , Colesterol/análise , Colesterol/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Insulina/análise , Insulina/sangue , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Resveratrol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Myocardial ischemiareperfusion (I/R) injury is a major cause of cardiovascular disease worldwide, and microRNAs have been implicated in the regulation of pathological and physiological processes in myocardial I/R injury. The present study aimed to investigate the role of microRNA (miR)2213p in myocardial I/R injury. Cell death and lactate dehydrogenase (LDH) activity were increased in hydrogen peroxide (H2O2)treated H9c2 cells, as measured by flow cytometry and an LDH detection kit. The expression of miR2213p was elevated in H2O2incubated cells and in remote areas of the rat I/R model, examined using reverse transcriptionquantitative polymerase chain reaction analysis. The overexpression of miR2213p enhanced the number of propidium iodide (PI)+ cells and the activity of LDH in H2O2treated cells. In I/Rinduced rats, the overexpression of miR2213p promoted the number of myosin+ cells and inhibited the fractional shortening of left ventricular diameter (FSLVD%). The results showed that the expression of p57 at the gene and protein levels was decreased in H9c2 cells incubated with H2O2 and in rats subjected to I/R surgery; the expression of p57 decreased following the overexpression of miR2213p. Subsequently, the hypothesis that p57 was the direct target of miR2213p was confirmed by performing a dualluciferase reporter assay. Finally, to examine the function of p57 in myocardial impairment, p57 was transfected into H9c2 cells and administered to the rats prior to undergoing H2O2 treatment and I/R surgery, respectively. The results indicated that p57 attenuated the number of PI+ cells and the activity of LDH in H2O2treated cells, whereas p57 downregulated the number of myosin+ cells and upregulated FSLVD% in the I/Rtreated rats. Therefore, these findings suggested that miR2213p exacerbated the H2O2induced myocardial damage in H9c2 cells and myocardial I/R injury in the rat model by modulating p57.