title: Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Endocrinology, Xiangya Hospital of Central South University, Hunan Province, Xiangya Street 78, Changsha 410008, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chun
authors.forename: Zhou
authors.initials: Z
authors.lastname: Junlin
authors.forename: Wang
authors.initials: W
authors.lastname: Aimin
authors.forename: Li
authors.initials: L
authors.lastname: Niansheng
authors.forename: Chen
authors.initials: C
authors.lastname: Benmei
authors.forename: Lei
authors.initials: L
authors.lastname: Minxiang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D015153:Blotting, Western; D002518:Ceramides / Q000097:blood* / Q000378:metabolism*; D002853:Chromatography, Liquid; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002518:Ceramides; D005229:Fatty Acids, Monounsaturated; D009569:Nitric Oxide; C001996:thermozymocidin