title: [Effects and related mechanisms of ghrelin on myocardial neovascularization in diabetic rats with experimental myocardial infarction].
abstract: OBJECTIVE
  To investigate the effects and related mechanisms of ghrelin on myocardial neovascularization in diabetic rats with experimental myocardial infarction (MI).
  
  
  METHODS
  Adult male SD rats were divided into six groups (n = 20 each group): control, diabetes mellitus (DM), MI, DM+MI, DM+MI+ghrelin, DM+MI+ghrelin+D-Lys3-GHRP-6 (GHSR1a inhibitor). DM was induced by streptozotocin (STZ, 60 mg/kg), 3 months later, MI was induced by left anterior descending artery ligation in DM rats. DM+MI+ghrelin group received ghrelin 200 µg×kg(-1)×d(-1) and DM+MI+ghrelin+D-Lys3-GHRP-6 group received ghrelin 200 µg×kg(-1)×d(-1) and D-Lys3-GHRP-6 50 mg×kg(-1)×d(-1) for 4 weeks. Then, cardiac function was measured by echocardiography, microvascular density (MVD) was measured by CD34 immunohistochemistry, myocardial infarct size was determined by Masson staining, the mRNA and protein expressions of vascular endothelial growth factor (VEGF) and receptors Flk-1, Flt-1 were detected by real-time PCR and Western-blot, respectively.
  
  
  RESULTS
  Compared with MI group, MVD (15.3 ± 1.0 vs.20.7 ± 1.6, P < 0.05), left ventricular ejection fraction (LVEF) ((64.2 ± 3.4)% vs. (81.3 ± 3.8)%, P < 0.01), left ventricular fractional shortening (LVFS) ((31.7 ± 1.1)% vs. (48.8 ± 3.3)%, P < 0.01) and the mRNA and protein expression of VEGF, Flk-1 and Flt-1 (P < 0.01) were reduced, while myocardial infarct size ((55.8 ± 3.1)% vs. (35.7 ± 2.5)%, P < 0.01) was increased in DM+MI group. These effects were partly reversed in DM+MI+ghrelin group and the beneficial effects of ghrelin were partly abolished by D-Lys3-GHRP-6 (all P < 0.05).
  
  
  CONCLUSIONS
  Our results demonstrate that ghrelin could improve microvascular density, cardiac function, and reduce myocardial infarct size of diabetic rats with myocardial infarction via modulating GHSR1a-mediated expressions of VEGF, Flk-1 and Flt-1.
authors.affiliation: Department of Geriatrics Cardiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Geriatrics Cardiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Email: chenqwcq@163.com.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Geriatrics Cardiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Ke
authors.affiliation: Department of Geriatrics Cardiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Guiqiong
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Geriatrics Cardiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003331:Coronary Vessels; D003921:Diabetes Mellitus, Experimental; D004452:Echocardiography; D054439:Ghrelin / Q000502:physiology*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D009206:Myocardium; D018919:Neovascularization, Physiologic; D009842:Oligopeptides; D051381:Rats; D042461:Vascular Endothelial Growth Factor A; D016277:Ventricular Function, Left
chemical_list: C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A