Sevoflurane Exposure of Clinical Dose in Pregnant Rat Induces Vcan Changes Without Significant Neural Apoptosis in the Offspring

Abstract Background: Sevoflurane is a commonly used inhalational anesthetic in clinic. Prolonged exposure to sevoflurane can induce significant changes in lipid metabolism and neuronal damage in the developing brain. However, the effect of sevoflurane exposure of clinical dose in pregnant rat remains unclear. Results: The following study was to explore lipidomics and transcriptomics changes related to 2% sevoflurane exposure for 6h in the developing brain of newborn offspring rats. UPLC/TOF-MS(Ultra Performance Liquid Chromatography/Time-Of-Flight Mass Spectrometry) and RNA-seq analysis was used to acquire metabolomics and transcriptomics profiles. We used RNA sequencing (RNA-seq) to analyze the expression of the coding and non-coding transcripts in neural cells of cerebral cortex. No significant differences in arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), arterial blood gas were found between groups. RSDs(Relative Standard Deviation) of retention times were < 1.53%, and RSDs of peak areas ranged from 2.13% to 8.51%. BPC profiles showed no differences between groups. We evaluated the Partial Least Square-Discriminant Analysis (PLS-DA) model: in negative ion mode: R2X, over 70%: R2Y, over 93%: Q2 (cum), over 80%; Cell apoptosis was not remarkably enhanced by TUNEL and HE staining in sevoflurane exposure in comparison to control group(P>0.05). Glycerophospholipid and sphingolipid metabolism disturbance might have adverse influence on neurodevelopment in offspring. The expression of mRNAs (Vcan gene, related to neuronal development, function, and repair) of sevoflurane group were significantly increased in the differential genes by qRT-PCR verification. Conclusions: glycerophospholipid and sphingolipid metabolism homeostasis may be potential therapeutic approaches against inhalational anesthetics-induced neurodegenerative disorders. Meanwhile, sevoflurane induced Vcan changes, which indicate some lipidomics and transcriptomics changes was happened even if neural cell apoptosis was not significantly changed in usual clinical dose of sevoflurane exposure.