Myocardial dysfunction is an important manifestation of
sepsis. Previous studies suggest that
melatonin is protective against
sepsis. In addition, activation of the
phosphatidylinositol 3-kinase (PI3K)/
protein kinase B (Akt) signaling pathway has been reported to be beneficial in
sepsis. However, the role of PI3K/Akt signaling in the protective effect of
melatonin against
sepsis-induced myocardial dysfunction remains unclear. Here,
LY294002, a PI3K inhibitor, was used to investigate the role of PI3K/Akt signaling in mediating the effects of
melatonin on
sepsis-induced myocardial injury. Cecal
ligation and
puncture (CLP) surgery was used to establish a rat model of
sepsis.
Melatonin was administrated to rats intraperitoneally (30 mg/kg). The survival rate, measures of myocardial injury and cardiac performance, serum
lactate dehydrogenase level, inflammatory
cytokine levels, oxidative stress level, and the extent of myocardial apoptosis were assessed. The results suggest that
melatonin administration after CLP surgery improved survival rates and cardiac function, attenuated myocardial injury and apoptosis, and decreased the serum
lactate dehydrogenase level.
Melatonin decreased the production of the inflammatory
cytokines TNF-α, IL-1β, and
HMGB1, increased
anti-oxidant enzyme activity, and decreased the expression of markers of oxidative damage. Levels of phosphorylated Akt (p-Akt), unphosphorylated Akt (Akt), Bcl-2, and Bax were measured by Western blot.
Melatonin increased p-Akt levels, which suggests Akt pathway activation.
Melatonin induced higher Bcl-2 expression and lower Bax expression, suggesting inhibition of apoptosis. All protective effects of
melatonin were abolished by
LY294002, the PI3K inhibitor. In conclusion, our results demonstrate that
melatonin mitigates myocardial injury in
sepsis via PI3K/Akt signaling activation.