Abstract
Objective:
To investigate the possible role of Naringenin in AMPK signaling pathway in LPS-induced septic cardiac dysfunction in mice and to elucidate the inherent mechanism.
Methods:
Male C57 mice were used in the establishment of mouse sepsis model. The effect of Naringenin on septic cardiac dysfunction was observed. Echocardiographic parameters were recorded. Western blot was employed to detect the expressions of BCL-2, BAX, cleaved caspase-3, pNF-kB and IkB-α. Myocardial mitochondria were isolated and extracted. Real-time PCR was applied to detect the expressions of Cox4i, Cox5a mRNA, mt-Nd1, mt-Nd2, mt-Co1 and mt-Co2 mRNA. Western blot was employed to detect the expressions of Complex I, Complex II, and OPA1 to evaluate the effects of Naringenin on myocardial mitochondrial biology and function in septic cardiac dysfunction.
Results:
The expressions of TNF-α, IL-6, pNF-κB and IκB-α have changed after Naringenin treatment. IκB-α expression was decreased, expressions of TNF-α, IL-6 and pNF-κB were increased. Naringenin has significantly inhibited AMPK and ACC phosphorylation, and decreased PGC1α expression. Moreover, Naringenin reversed the increased expressions of PGC1α and phosphorylation of AMPK and ACC by U75302 treatment, and decreased the expressions of complex I, complex II and OPA1.
Conclusion:
Naringenin inhibits LTB4/BLT1 receptors to attenuate cardiomyocyte inflammation and apoptosis, which may mediate the protective effect of anti-septic cardiac dysfunction by activating AMPK signaling pathway and inhibiting NF-κB signaling and mitochondrial damage.
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