[Selectively stimulating β1-adrenergic receptor attenuates rat myocardial ischemia/reperfusion injury in vivo by inhibiting high mobility group box 1 protein release].
OBJECTIVE
To investigate whether selectively stimulating β1-adrenergic receptor could inhibit high mobility group box 1 protein and attenuate myocardial ischemia/reperfusion(I/R) injury in rats.


METHODS
Eighty healthy male Sprague-Dawley (SD) rats were randomly divided into seven groups: (1) Sham operated group (SO); (2) Ischemia/reperfusion (I/R) group; (3) Dobutamine1 (5 µg×kg⁻¹ · min⁻¹) + I/R group; (4) Dobutamine2 (10 µg·kg⁻¹ × min⁻¹) + I/R group; (5) LY294002 (0.3 mg/kg) + Dobutamine2 + I/R group; (6) SB203580 (1 mg/kg) + Dobutamine2 + I/R group; (7) ZnPPIX (10 mg/kg) + Dobutamine2+I/R group. Rats were pretreated by saline, dobutamine, LY294002, SB203580 and ZnPPIX, respectively, then underwent myocardial I/R. Myocardial I/R injury and oxidative stress were assessed, and myocardial HO-1, NF-κB and HMGB1 expressions were measured by Western blot analysis.


RESULTS
Dobutamine significantly reduced the myocardial infarct size (P < 0.05), myocardial enzymes (LDH and CK) (P < 0.05) and proinfiammation cytokines (TNF-α and IL-6), reduced oxidative stress (MDA and SOD) in a dose-dependent manner (all P < 0.05). Meanwhile, dobutamine significantly and dose-dependently mediated the induction of HO-1 (P < 0.05), the expression of NF-κB (P < 0.05) and HMGB1 (P < 0.05). However, all the effects could be significantly reversed by co-treatment with LY294002, SB203580 and ZnPPIX (all P < 0.05).


CONCLUSIONS
Current study demonstrates that selectively stimulating β1-adrenergic receptor by dobutasmine could reduce rat myocardial I/R injury in vivo through promoting the induction of HO-1 and inhibiting HMGB1 release.
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China.
Jichun
J
Wang
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China.
Xiaorong
X
Hu
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China.
Jing
J
Xie
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China.
Xiaoya
X
Zhou
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China. Email: jianghongwhu@163.com.
Hong
H
Jiang
D000818:Animals; D002867:Chromones; D004280:Dobutamine; D024243:HMGB1 Protein / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles; D015850:Interleukin-6; D008297:Male; D009025:Morpholines; D009203:Myocardial Infarction; D017202:Myocardial Ischemia; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D009206:Myocardium; D016328:NF-kappa B; D018384:Oxidative Stress; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic; D015427:Reperfusion Injury; D013482:Superoxide Dismutase; D014409:Tumor Necrosis Factor-alpha
D002867:Chromones; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D007093:Imidazoles; D015850:Interleukin-6; D009025:Morpholines; D016328:NF-kappa B; D011725:Pyridines; D011941:Receptors, Adrenergic; D014409:Tumor Necrosis Factor-alpha; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004280:Dobutamine; D013482:Superoxide Dismutase; C093642:SB 203580