The hest interventional time of α7nAChR agonist postconditioning attenuating myocardial ischemia/reperfusion injury in rats

Abstract

Objective To determine the best interventional time of α7nAChR agonist postconditioning for attenuating myocardial ischemia reperfusion injury in rat in vivo model. Methods Sixty SD rats were randomly divided into six groups(n=10):sham group (S group), ischemia/reperfusion group (I/R group ), α7nAChR agonist postconditioning at onset of reperfusion group( P0group), α7nAChR agonist postconditioning at 30, 60 and 90 min of reperfusion group(P30, P60 and P90 groups). Serum concentrations of TnI, TNF-α and HMGB1 were assayed at 180 min after reperfusion. At the end of experiment, infarction sizes were assessed from excised hearts by Evans blue and triphenyltetrazolium chloride(TTC) staining. Results The infarct sizes(IS％) were (78±16)％ in IR group, (60±7)％ in P0 group, (49±17)％ in P30 group, (54±12)％ in P60 group and (64±15)％ in P90 group, respectively. Serum concentrations of TnI were ( 1.016±0.121 ), (0.168±0.037), (0.156±0.019), (0.194±0.041) and(0.138±0.029) μg/L in these groups respectively. As compared to the S group, serum concentrations of TNF-α in the I/R and P30 groups were significantly increased,TNF-α in the P0 group was significantly reduced. Serum concentration of HMGB1 was significantly higher in the I/R group than that in the S group, but that of all α7nAChR agonist postconditioning groups was significantly lower. As compared with the I/R group, infarct size and serum concentrations of TnI, TNF-α and HMGB1 in all α7nAChR agonist postconditioning groups were significantly reduced. As compared with the P0group, serum concentrations of TNF-α and HMGB1 in the P30, P60 and P90 groups were significantly increased. As compared with the P90 group, in the P30 group, serum concentrations of TNF-α and HMGB1 were significantly increased and IS％ significantly decreased. Conclusion In rat in vivo models of myocardial ischemia reperfusion injury, α7nAChR agonist postconditioning at 30 min of reperfusion could produce the strongest cardioprotection. Key words: Ischemia/reperfusion injury; α7nAChR; Inflammation; Pharmacological postconditioning