title: Imbalance of glomerular VEGF-NO axis in diabetic rats: prevention by chronic therapy with propyl gallate.
abstract: BACKGROUND
  The uncoupling of the vascular endothelial growth factor-nitric oxide (VEGF-NO) axis may play a vital role in inducing glomerular endothelial dysfunction. We investigate the factors that contribute to the imbalance of the VEGF-NO axis and evaluate the effect of propyl gallate on preventing endothelial dysfunction.
  
  
  METHODS
  Streptozotocin (STZ, 60 mg/kg) was administrated to rats to establish an animal diabetic nephropathy model. The diabetic rats were randomly divided into a diabetic model group and a propyl gallate-treated group. Animals were sacrificed 8 weeks after the model was established. Periodic acid-Schiff staining was conducted to observe pathological changes, and reverse transcriptase polymerase chain reaction and Western blot were employed to analyze endothelial nitric oxide synthase (eNOS) and VEGF expressions. Commercial kits were used to detect glomerular eNOS activity and NO production, as well as oxidative stress.
  
  
  RESULTS
  Compared with that in the normal control group, glomerular eNOS activity significantly decreased in diabetic rats, but eNOS expression remained at the same level. The expression of VEGF increased at this stage. Levels of glomerular oxidative stress also increased in diabetic rats and were inversely correlated with eNOS activity. Treatment with propyl gallate restored eNOS activity, ameliorated oxidative stress and improved glomerular pathological changes, but did not alter eNOS and VEGF expressions.
  
  
  CONCLUSIONS
  The imbalance of the VEGF-NO axis in the glomeruli of diabetic rats may have resulted from eNOS inactivation, but not from the decrement in eNOS expressions at the early stage of rat diabetic nephropathy. Propyl gallate improved glomerular pathological changes in diabetic rats, possibly through oxidative stress reduction and VEGF-NO axis recovery.
authors.affiliation: Department of Nephrology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. shaojiangt@yahoo.com.cn
authors.forename: Shaojiang
authors.initials: S
authors.lastname: Tian
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Gan
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Jianming
authors.initials: J
authors.lastname: Shen
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Tingting
authors.initials: T
authors.lastname: Ye
authors.forename: Huihui
authors.initials: H
authors.lastname: Liu
authors.forename: Dianjun
authors.initials: D
authors.lastname: Liu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Deng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D011435:Propyl Gallate / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D008315:Malondialdehyde; D013311:Streptozocin; D011435:Propyl Gallate; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005978:Glutathione