Molecular Mechanism of Sevoflurane Preconditioning Based on Whole-transcriptome Sequencing of Lipopolysaccharide-induced Cardiac Dysfunction in Mice.

Abstract

Sevoflurane, a widely used inhalation anesthetic, has been shown to be cardioprotective in individuals with sepsis and myocardial dysfunction. However, the exact mechanism has not been completely explained. In this study, we performed whole-transcriptome profile analysis in the myocardium of lipopolysaccharide-induced septic mice after sevoflurane pretreatment. RNA transcriptome sequencing showed that 97 protein coding RNAs (mRNAs), 64 long noncoding RNAs (lncRNAs), and 27 microRNAs (miRNAs) were differentially expressed between the lipopolysaccharide and S_L groups. Functional enrichment analysis revealed that target genes for the differentially expressed mRNAs between the 2 groups participated in protein processing in the endoplasmic reticulum, antigen processing and presentation, and the mitogen-activated protein kinase signaling pathway. The bioinformatics study of differentially expressed mRNAs revealed that 13 key genes including Hsph1, Otud1, Manf, Gbp2b, Stip1, Gbp3, Hspa1b, Aff3, Med12, Kdm4a, Gatad1, Cdkn1a, and Ppp1r16b are related to the heart or inflammation. Furthermore, the competing endogenous RNA network revealed that 3 of the 13 key genes established the lncRNA-miRNA-mRNA network (ENSMUST00000192774 --- mmu-miR-7a-5p --- Hspa1b, TCONS_00188587 --- mmu-miR-204-3p --- Aff3 and ENSMUST00000138273 --- mmu-miR-1954 --- Ppp1r16b) may be associated with cardioprotection in septic mice. In general, the findings identified 11 potential essential genes (Hsph1, Otud1, Manf, Gbp2b, Stip1, Gbp3, Hspa1b, Aff3, Med12, Kdm4a, Gatad1, Cdkn1a, and Ppp1r16b) and mitogen-activated protein kinase signaling pathway involved in sevoflurane-induced cardioprotection in septic mice. In particular, sevoflurane may prevent myocardial injury by regulating the lncRNA-miRNA-mRNA network, including (ENSMUST00000192774-mmu-miR-7a-5p-Hspa1b, TCONS_00188587-mmu-miR-204-3p-Aff3, and ENSMUST00000138273-mmu-miR-1954-Ppp1r16b networks), which may be a novel mechanism of sevoflurane-induced cardioprotection.