α7nAChR agonist postconditioning attenuates rat myocardia ischemia reperfusion injury in vivo

Abstract

Objective To observe the cardioprotective effects of α7 nicotinic acetylcholine receptor (α7nAChR) agonist postconditioning on myocardial ischemia reperfusion injury (IRI) in rat models in vivo. Methods Forty SD rats were randomly divided into four groups (n=10): sham group( S group), ischemia reperfusion group( IR group), ischemia preconditioning group( IPC group) and α7nAChR agouist postconditioning group (PNU group). Incidence of arrhythmia was recorded during the period of ischemia and onset of reperfusion. Serum concentrations of tumor necrosis factor-o(TNF-α), interlerkin-6(IL-6) were assayed at 30 min and 180 min after reperfusion, and serum concentrations of high mobility group box 1 protein(HMGB1 ) and troponin I(TnI) at 180 min after reperfusion were tested in all groups. At the end of experiment, infarction sizes were assessed from excised hearts by Evans blue and 1 % triphenyltetrazolium chloride staining. Results The infarct size(IS%) of IR,IPC and PNU groups were(78.4±16.1 )%, (35.3±9.4)%and (60.4±7.0)% respectively,and the serum concentration of TnI in these groups were (1.02±0.12) μg/L,(0.25±0.03) μg/L and (0.17±0.04) μg/L. respectively. Compared to IR group, the IS% and serum concentration of TnI in IPC group and PNU group were significantly reduced. The serum concentrations of TNF-α and IL-6 at 30 min of reperfusion and TNF-α and HMGBI at 180 min of reperfusion in IPC group and PNU group were significantly lower than these in IR group. And the serum level of IL-6 at 180 min of reperfusion in PNU group was also significantly decreased compared to IR group. Compared to IPC group, the infarct size of PNU group was significantly increased, however the serum concentration of TnI of PNU group was significantly decreased. Although the serum concentration of IL-6 at 30 min of reperfusion in PNU group was significantly higher than that in IPC group, the serum concentrations of TNF-α at 30 min of re perfusion and TNF-α, IL-6 and HMGB1 at 180 min of reperfusion were significantly decreased. Conclusion In rat in vivo models of myocardial ischemia reperfusion injury, α7nAChR agonist postconditioning could inhibit the reperfusion-induced inflammatory response to realize the cardioprotection. However the effect of infarct size limiting induced by α7nAChR postconditioning is less powerful than that of ischemia preconditioning. Key words: Ischemia reperfusion injury; Ischemia preconditioning; α7nAChR agonist postconditioning; Cholinergic anti-inflammatory pathway; Inflammation