[Selectively stimulating β1-adrenergic receptor attenuates rat myocardial ischemia/reperfusion injury in vivo by inhibiting high mobility group box 1 protein release].

Abstract

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.

• Authors: Jichun Wang, Xiaorong Hu, Jing Xie, Xiaoya Zhou, Hong Jiang
• Journal: Zhonghua xin xue guan bing za zhi (Zhonghua Xin Xue Guan Bing Za Zhi) Vol. 42 Issue 8 Pg. 680-5 (Aug 2014) ISSN: 0253-3758 [Print] China
• PMID: 25388343 (Publication Type: Journal Article)

Chemical References

• Chromones
• HMGB1 Protein
• Hbp1 protein, rat
• Imidazoles
• Interleukin-6
• Morpholines
• NF-kappa B
• Pyridines
• Receptors, Adrenergic
• Tumor Necrosis Factor-alpha
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Dobutamine
• Superoxide Dismutase
• SB 203580

Topics

• Animals
• Chromones
• Dobutamine
• HMGB1 Protein (drug effects, metabolism)
• Imidazoles
• Interleukin-6
• Male
• Morpholines
• Myocardial Infarction
• Myocardial Ischemia
• Myocardial Reperfusion Injury (drug therapy, metabolism)
• Myocardium
• NF-kappa B
• Oxidative Stress
• Pyridines
• Rats
• Rats, Sprague-Dawley
• Receptors, Adrenergic
• Reperfusion Injury
• Superoxide Dismutase
• Tumor Necrosis Factor-alpha