Effects and related mechanisms of ghrelin on myocardial neovascularization in diabetic rats with experimental myocardial infarction
10.3760/cma.j.issn.0253-3758.2014.09.012
- VernacularTitle:ghrelin对糖尿病大鼠缺血诱导的血管新生障碍的影响及相关机制
- Author:
Li WANG
1
;
Qingwei CHEN
;
Dazhi KE
;
Guiqiong LI
;
Zhiqin WU
Author Information
1. 400010,重庆医科大学附属第二医院老年心血管科
- Keywords:
Diabetes mellitus;
Myocardial infarction;
Neovascularization,pathologic;
Receptors,somatotropin
- From:
Chinese Journal of Cardiology
2014;42(9):765-772
- CountryChina
- Language:Chinese
-
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 (GHSRla 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 GHSR1 a-mediated expressions of VEGF,Flk-1 and Flt-1.
