Postoperative cognitive dysfunction (POCD) is deemed to a severe surgical complication without effective treatment. Previous work has confirmed the important modulatory role of
hydrogen sulfide (H2S) in cognitive function. This study was proposed to explore whether H2S relieves POCD and the possible mechanisms. We demonstrated that
NaHS (a donor of H2S) reversed the inhibited endogenous H2S generation in the hippocampus of postoperative rats.
NaHS attenuated the
cognitive impairment of postoperative rats in the Y-maze, Novel object recognition, and Morris water maze tests.
NaHS enhanced the expressions of synaptic plasticity-related
proteins, synapsin-1 and PSD-95, increased the synaptic density, and decreased the destruction of synaptic structures in the hippocampus of postoperative rats. Moreover,
NaHS promoted Warburg effect in the hippocampus of postoperative rats, as reflected by increases in the expressions of
hexokinase 2,
pyruvate kinase M2,
lactate dehydrogenase A, and
pyruvate dehydrogenase kinase 1, an enhancement in the content of
lactate, and a reduction in the expression of
pyruvate dehydrogenase. The inhibitor of Warburg effect,
2-Deoxy-D-glucose (2-DG), not only reversed
NaHS-enhanced Warburg effect in the hippocampus of postoperative rats, but also significantly abolished
NaHS-exerted protective effect on cognitive function. Furthermore, 2-DG reversed
NaHS-exerted enhancement in the expressions of synapsin-1 and PSD-95, increase in the synaptic density, and decrease in the destruction of synaptic structures in the hippocampus of postoperative rats. Collectively, these results indicate that H2S alleviates POCD through enhancing hippocampal Warburg effect, which subsequently improves synaptic plasticity in the hippocampus.