title: Exendin-4 attenuates myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein expression.
abstract: BACKGROUND
  High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia and reperfusion (I/R) injury. Exendin-4 (Ex-4), glucagon-like peptide-1 receptor agonist, has been reported to attenuate myocardial I/R injury. This study was to investigate the potential mechanism by which Ex-4 attenuates myocardial I/R injury in rats.
  
  
  METHODS
  Anesthetized male rats were once treated with Ex-4 (5 μg/kg, i.v.) 1 h before ischemiain the absence and/or presence of exendin (9-39) (an antagonist for glucagon-like peptide-1 receptor, 5 μg/kg, i.v.), and then subjected to ischemia for 30 min followed by reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) activity and infarct size were measured. HMGB1 expression was assessed by immunoblotting.
  
  
  RESULTS
  The results showed that pretreatment of Ex-4 could significantly decrease the infarct size and the levels of LDH and CK after 4 h reperfusion (all p < 0.05). Ex-4 could also significantly inhibit the increase of the MDA level, the decrease of the SOD level (both p < 0.05). Meanwhile, Ex-4 could significantly inhibit HMGB1 expression induced by I/R. Administration of exendin (9-39) could abolish the protective effect of Ex-4 (all p < 0.05).
  
  
  CONCLUSIONS
  The present study suggested that Ex-4 could attenuate myocardial I/R injury which may be associated with inhibiting HMGB1 expression.
authors: Gangying
authors: G
authors: Hu
authors: Yijie
authors: Y
authors: Zhang
authors: Hong
authors: H
authors: Jiang
authors: Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute of Wuhan University, Wuhan, China Department of Cardiology, Huangshi Central Hospital, Afilliated Hospital of Hubei Polytechnic University, Huangshi, China. huxrwurm@163.com.
authors: Xiaorong
authors: X
authors: Hu
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D015536:Down-Regulation; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D024243:HMGB1 Protein / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014688:Venoms / Q000494:pharmacology*
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D010446:Peptide Fragments; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D008315:Malondialdehyde; C083773:exendin (9-39); D000077270:Exenatide; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase