Melatonin alleviates myocardial ischemia-reperfusion injury in mice by inhibiting inflammatory response via activating Nrf2 signaling

Objective: To investigate the protective effect of melatonin against myocardial ischemia-reperfusion (IR) injury in mice and the role of Nrf2 signaling in mediating this effect.

Methods: C57/bl6 mice were randomized into sham-operated group(Sham), IR group(IR), IR with melatonin treatment(melatonin+IR)group, and IR with melatonin and Nrf2 inhibitor ML-385 (melatonin+ML-385+IR) group.In the latter 3 groups, mouse models of myocardial IR injury were established by ligation of the left anterior descending coronary artery.The infarct size was measured with Evans blue/TTC staining, and serum LDH level was detected using ELISA.The ejection fraction (EF) and fractional shortening (FS) of the mice were measured using Vevo software.The expressions of Bcl2, Bax, Nrf2, Nrf2 substrates NQO-1 and HO-1, TNF-α, IL-1β, and IL-6 in the myocardial tissues were detected with Western blotting.

Results: Compared with the sham-operated mice, the mouse models of myocardial IR injury showed significantly increased infarct size and serum LDH levels (P < 0.01) with obviously decreased EF and FS (P < 0.01).The mouse models also showed significantly increased expressions of Bax, TNF-α, IL-1β and IL-6, decreased expression of Bcl2, Nrf2, NQO-1, and HO-1, and increased apoptotic index and TNF-α expression in the myocardial tissue(P < 0.01).Melatonin treatment significantly decreased the infarct size, serum LDH levels, the expressions of Bax, TNF-α, IL-1β and IL-6(P < 0.01), lowered the apoptotic index, and increased the expressions of Bcl2, Nrf2, NQO-1, and HO-1 in the mouse models(P < 0.01).The effects of melatonin were obviously blocked by ML-385 treatment in the mouse models.

Conclusion: Melatonin can alleviate myocardial IR injury in mice by inhibiting inflammatory response via activation of Nrf2 signaling.