Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats

Abstract

ObjectivesTo explore the effect of myriocin on EDVD and atherosclerosis in diabetic rats. MethodsRats were fed with a high-fat/high-sucrose/high-cholesterol diet (20% sucrose, 10% animal oil, 1.0% bile salt and 2.5% cholesterol) (hereinafter defined as diabetic groups) or Purina Rodent Chow (NC group), the former was intervened with low dose streptozotocin (30mg/kg) after feeding 1 month to make diabetic model. The NC group was intervened with citrate buffer and the diabetic rats were intervened with myriocin (0.3mg/kg Qod) (MTD group) or just solvent (DC group) for 14 weeks. The EDVD, thickness of fatty deposition under endothelium, ceramide, PI3K/PKB/eNOS, NO and other vital parameters were measured after the rats sacrificed. ResultsIn DC group, the ceramide contents in serum and aorta increased, the EDVD was impaired, the fatty deposition under endothelium increased, and the phosphorylation of PI3K/PKB/eNOS and NO release decreased all compared with the NC group (P<0.05). Compared with the DC group, the ceramide contents in MTD group decreased, the EDVD ameliorated, the fatty deposition diminished, and PI3K/PKB/eNOS phosphorylation and NO release (P<0.05) increased. ConclusionsAfter treated with myriocin, the EDVD in diabetic rats has been improved by increasing PI3K/PKB/eNOS phosphorylation and NO release, and meanwhile the atherosclerosis has reversed.