title: The protective role of hydrogen sulfide in myocardial ischemia-reperfusion-induced injury in diabetic rats.
abstract: BACKGROUND
  Hydrogen sulfide (H(2)S) displays anti-inflammatory and cytoprotective activities to attenuate myocardial ischemia-reperfusion (MIR)-induced injury, but its role in MIR in diabetics is not known. This study was undertaken to investigate whether H(2)S plays a protective role in MIR in diabetic rats.
  
  
  METHODS
  Diabetes was induced by streptozocin in Wistar rats, which were subjected to myocardial ischemia by blocking the left circumflex artery for 30 min, followed by 2h reperfusion. dl-propargylglycine (PAG) and sodium hydrosulfide (NaHS) were administered to the rats to investigate their effects on severity of MIR-induced injury.
  
  
  RESULTS
  Diabetic rats had smaller myocardial infarct sizes and higher serum levels of H(2)S (both P < 0.05) than non-diabetics when they underwent MIR. MIR significantly increased the serum level of H(2)S (49.5 ± 7.1 μM), H(2)S-synthesizing activity (7.4 ± 1.6 nmol/mg) and the myocardial infarct size (44.0 ± 7.2%), compared with sham-operated diabetic rats (21.7 ± 2.1 μM, 0.15 ± 0.4 nmol/mg and 1.2 ± 0.4%, respectively). Administration of NaHS increased the H(2)S level (65.8 ± 6.9 μM) and had little effect on H(2)S production activity (6.5 ± 2.2 nmol/mg), while PAG reduced both the H(2)S level (29.2 ± 5.0 μM) and H(2)S-synthesizing activity (2.2 ± 1.8 nmol/mg). NaHS significantly reduced the myocardial infarct size (31.2 ± 4.7%), inhibited the production of lipid peroxidation, MPO activity, and cell apoptosis, and downregulated expression of caspase-3, Fas, FasL, and TNF-α, which had been elevated by MIR, while PAG further increased the myocardial infarct size (58.3 ± 5.9%), and displayed opposite effects.
  
  
  CONCLUSIONS
  The study indicates that H(2)S may play a protective role in MIR-induced myocardial injury in diabetics by its anti-apoptotic, anti-oxidative and anti-inflammatory activities.
authors.affiliation: Department of ICU, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Yao
authors.forename: Yina
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.forename: Xueying
authors.initials: X
authors.lastname: Sun
mesh_terms: D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000097:blood / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013440:Sulfides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000480:Alkynes; D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; C491898:Fas protein, rat; C505662:Faslg protein, rat; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C009055:propargylglycine; D009195:Peroxidase; D053148:Caspase 3; C025451:sodium bisulfide; D005998:Glycine; D006862:Hydrogen Sulfide