title: Intermittent hypoxia-induced rat pancreatic β-cell apoptosis and protective effects of antioxidant intervention.
abstract: OBJECTIVE
  Obstructive sleep apnea hypopnea syndrome (OSAHS), a common sleep and breathing disorder, is independently associated with metabolic dysfunction, including impaired glucose tolerance and insulin resistance. Intermittent hypoxia (IH), a pathological component of OSAHS, increases oxidative stress damage to pancreatic β-cells in animal models resembling patients with OSAHS. However, the precise mechanisms of IH-induced pancreatic β-cell dysfunction are not fully understood. In the present study, we established a mice model to investigate the underlying mechanisms of oxidative stress in IH-induced pancreatic β-cell apoptosis through antioxidant N-acetylcysteine (NAC) pretreatment.
  
  
  METHODS
  Twenty-four Wistar rats were randomly divided into four experimental groups: normal control group, intermittent normoxia group, IH group and antioxidant intervention group. Pancreatic β-cell apoptosis rates were detected by terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling; Bcl-2 and Bax protein expressions were detected by immunohistochemistry staining and western blotting.
  
  
  RESULTS
  In our study, we demonstrated that IH exposure causes an increased activation of pancreatic β-cell apoptosis compared with that in the normal control group and intermittent normoxia group, accompanied by the downregulation of Bcl-2 and upregulation of Bax (P<0.05). Furthermore, compared with the IH group, antioxidant (NAC) pretreatment significantly decreased IH-mediated β-cell apoptosis and reversed the ratio of Bcl-2/Bax expression (P<0.05).
  
  
  CONCLUSIONS
  Taken together, these results demonstrate a critical role of oxidative stress in the regulation of apoptosis through Bcl-2 and Bax signaling. The antioxidant NAC has a protective effect against IH-induced pancreatic β-cell apoptosis.Nutrition & Diabetes advance online publication, __PUBDATE__; doi:10.1038/nutd.2014.28.
authors.affiliation: Tianjin Medical University General Hospital, Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Tianjin Medical University General Hospital, Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University General Hospital, Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin, China.
authors.forename: J
authors.initials: J
authors.lastname: Tan
authors.affiliation: Tianjin Medical University General Hospital, Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Tianjin Medical University General Hospital, Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin, China.
authors.forename: X
authors.initials: X
authors.lastname: An
authors.affiliation: Tianjin Medical University General Hospital, Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin, China.
authors.forename: P
authors.initials: P
authors.lastname: Lei