Abstract
Background: General anaesthesia, especially sevoflurane inhalation anaesthesia, is an independent risk factor for postoperative cognitive dysfunction. However, the molecular mechanism by which sevoflurane inhalation alters postoperative cognitive function remains unclear.
Methods: According to the water maze behaviour experiment, sixteen-month-old mice receiving sevoflurane inhalation were divided into postoperative cognitive dysfunction and none cognitive dysfunction groups. Faecal samples were collected from two groups one day before intervention and 1, 3, and 7 days after. Moreover, hippocampal and serum samples were collected seven days after intervention. Faecal samples were analysed at the microbiome and metabolomics levels. The hippocampal samples were analysed using proteomics and metabolomics. Moreover, serum samples were analysed using metabolomics. Further, bioinformatics technology was used to integrate and analyse the omics.
Results: The significantly downregulated Ohtaekwangia (P=0.022) and Odoribacter (P=0.016) in the intestinal microbes of aged mice with ostoperative cognitive function had a significant positive correlation with the faecal metabolite, guanosine-5'-monophosphate (P=0.008). At the same time, guanosine-5-monophosphate showed the same downward trend in stool and serum samples. In addition, 1,7-dimethylxanthine was significantly downregulated in the hippocampus of aged mice with ostoperative cognitive function and was positively correlated with calpastatin, whose expression was downregulated (P=0.013).
Conclusions: Significant changes in microorganisms, proteins, and metabolites were detected in the faecal, serum, and hippocampal samples of aged mice with ostoperative cognitive function induced by sevoflurane inhalation. Moreover, there was a correlation between the three samples. These findings provide new insights into the mechanisms of ostoperative cognitive function.