title: Anti-inflammatory effect of exendin-4 postconditioning during myocardial ischemia and reperfusion.
abstract: High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia and reperfusion (I/R) injury. Preconditioning of exendin-4 (Ex), a glucagon-like peptide-1 receptor agonist, has been reported to attenuate myocardial I/R injury. The current study investigated whether Ex postconditioning also attenuated myocardial I/R injury and the potential mechanisms. Anesthetized male rats were subjected to ischemia for 30 min and treated with Ex (5 μg/kg, i.v.) 5 min before reperfusion, in the absence and/or presence of exendin (9-39) (an antagonist of glucagon-like peptide-1 receptor, 5 μg/kg, i.v.), followed by reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor-α, interleukin-6, and infarct size were measured. HMGB1 expression was assessed by immunoblotting. Postconditioning with Ex significantly decreased infarct size and levels of LDH and CK after 4 h reperfusion (all p < 0.05). Ex also significantly inhibited the increase in malondialdehyde level and decreased the level of superoxide dismutase (both p < 0.05). In addition, the increase in HMGB1 expression induced by I/R was significantly attenuated by Ex postconditioning. Administration of exendin (9-39) abolished the protective effect of Ex postconditioning (all p < 0.05). The present study suggests that Ex postconditioning may attenuate myocardial I/R injury, which may in turn be associated with inhibiting inflammation.
authors.affiliation: Department of Emergency, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, China.
authors.forename: Xianjin
authors.initials: X
authors.lastname: Du
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000096:biosynthesis; D000077270:Exenatide; D005786:Gene Expression Regulation / Q000187:drug effects; D000067757:Glucagon-Like Peptide-1 Receptor; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists* / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014688:Venoms / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D015850:Interleukin-6; D010446:Peptide Fragments; D010455:Peptides; D018027:Receptors, Glucagon; D014409:Tumor Necrosis Factor-alpha; D014688:Venoms; C083773:exendin (9-39); D000077270:Exenatide; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase