title: Chronic intermittent hypobaric hypoxia ameliorates diabetic nephropathy through enhancing HIF1 signaling in rats.
abstract: OBJECTIVE
  Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) had anti-diabetes effect. The present study was to explore the renal protective effect of CIHH in diabetic rats.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into three groups: diabetes mellitus group (DM, induced by high-fat diet combined with low-dose streptozotocin), diabetes plus CIHH treatment group (DM+CIHH, simulated 5000-m altitude, 6h per day for 28days, after diabetes model confirmed) and control group (CON). Systolic arterial blood pressure (SAP), blood biochemicals, urinary albumin, and histopathology of kidney were determined. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, protein levels of hypoxia induced factors (HIFs) and transforming growth factor β1 (TGF-β1) in kidney were assayed.
  
  
  RESULTS
  The increased SAP, urinary albumin, hyperplasia of glomerular, fibrosis in mesangial and glomerular, and abnormal lipid metabolism in diabetic rats were ameliorated by CIHH treatment. And decreased superoxide dismutase (SOD) activity and increased malondialdehyde (MDA) level in diabetic kidney were reversed in CIHH-treated DM rats. In addition up-regulated TGF-β1 and down-regulated HIF1α in diabetic kidney returned back to normal level in CIHH-treated DM rats.
  
  
  CONCLUSIONS
  These data demonstrated for the first time that CIHH had protective effects against the early stage damage of diabetic nephropathy through activating HIF1 signaling, improving anti-oxidation and inhibiting TGF-β1 signaling in diabetic rats.
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, PR China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Tian
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Physiology, Medical College, Hebei University, Baoding 071000, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, PR China.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Bethune International Peace Hospital, Shijiazhuang 050082, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, PR China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, PR China. Electronic address: zhyhenryphy@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000628:therapy*; D059305:Diet, High-Fat / Q000009:adverse effects; D005355:Fibrosis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007668:Kidney / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053773:Transforming Growth Factor beta1; D008315:Malondialdehyde; D013311:Streptozocin; D013482:Superoxide Dismutase
keywords: Anti-oxidation; Chronic intermittent hypobaric hypoxia; Diabetic nephropathy; Hypoxia-inducible factor; Transforming growth factor β