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

AbstractOBJECTIVES:
To explore the effect of myriocin on EDVD and atherosclerosis in diabetic rats.
METHODS:
Rats 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 (30 mg/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 (0.3 mg/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.
RESULTS:
In 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.
CONCLUSIONS:
After 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.
AuthorsLi Chun, Zhou Junlin, Wang Aimin, Li Niansheng, Chen Benmei, Lei Minxiang
JournalDiabetes research and clinical practice (Diabetes Res Clin Pract) Vol. 93 Issue 1 Pg. 77-85 (Jul 2011) ISSN: 1872-8227 [Electronic] Ireland
PMID21492950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Ceramides
  • Fatty Acids, Monounsaturated
  • Nitric Oxide
  • thermozymocidin
Topics
  • Animals
  • Atherosclerosis (blood, drug therapy, metabolism)
  • Blotting, Western
  • Ceramides (blood, metabolism)
  • Chromatography, Liquid
  • Diabetes Mellitus, Experimental (blood, drug therapy, metabolism)
  • Endothelium, Vascular (drug effects, pathology, ultrastructure)
  • Fatty Acids, Monounsaturated (therapeutic use)
  • Immunohistochemistry
  • Male
  • Mass Spectrometry
  • Microscopy, Electron, Transmission
  • Nitric Oxide (blood)
  • Rats
  • Rats, Sprague-Dawley

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