Identifying biomarkers of hepatic fatty acid metabolism disorder in sevoflurane-induced brain developmental injury by bioinformatics analysis

Haozheng Yuan ^1,2 Yuying Lv ³ Pei Fan ³ Pengyu Jia ³ Kui Wang ³ Kailing Hu ³ Haogong Sun ³ Xinlin Chen ⁴ Pengbo Zhang ^3*

• ¹ Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
• ² Department of Anesthesiology, Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi Province, China
• ³ Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi Province, China
• ⁴ Institute of Neurobiology, School of Basic Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China

Exposure to sevoflurane in neonatal rats disrupts energy metabolism during brain development, which is associated with anesthetic-induced neurodevelopmental toxicity. Hepatic fatty acid metabolism plays a critical role in response to brain energy supply. However, how sevoflurane exposure affect hepatic fatty acid metabolism remains unclear. In this study, multiple methods were used to analyze gene changes of hepatic fatty acid metabolism and immune cell infiltration after sevoflurane exposure in neonatal rats. Related-metabolic pathways and expression changes of DCHR24 in cholesterol metabolism were also deciphered. Significant differences were found in the expression levels of differentially sequenced genes and 15 fatty acid metabolism-related differential expressed genes between the two groups. A total of 40 genes related to gene ontology (GO) and 5 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) were significantly enriched. Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) showed that 130 GO gene sets and 5 KEGG pathways were significantly up-regulated, while 62 GO gene sets and 2 KEGG pathways were significantly down-regulated. According to the Friends analysis, Dhcr24 may play a more critical role in the pathway. The analysis of mRNA-miRNA-lncRNA networks revealed that certain genes in lncRNA and mRNA played crucial roles in the regulatory network. A total of 43 key gene-drug small molecule combinations with significant differences in IC50 were identified. Bioinformatics analysis identified effective diagnostic biomarkers for fatty acid metabolism and immune cell infiltration in rat liver after sevoflurane exposure. These findings provide a basis for searching for more specific targets against the neurodevelopmental toxicity of sevoflurane.