We have already known sevoflurane has myocardial protective effects. DEGs between before inhalation (baseline sevoflurane) and after inhalation (sevoflurane) samples based on gene expression profiling data were screened out from the GEO database. Finally, we identified 297 upregulated DEGs and 429 downregulated DEGs. The GO annotation analysis of those selected DEGs shows that BP terms including positive regulation of endothelial cell migration, positive regulation of transcription from RNA polymerase II promoter and transcription, DNA-templated, MFs terms including transcription factor activity, sequence-specific DNA binding, protein binding, sequence-specific DNA binding and DNA binding and CCs including the nucleus. KEGG pathway analysis showed that DEGs were mainly enriched in pathways in the PI3K-Akt signaling pathway, MAPK signaling pathway, Rap1 signaling pathway, TNF signaling pathway, and Neurotrophin signaling pathway, and so on. A PPI network was constructed to investigate the interrelationship of the DEGs, and ten hub genes were identified, including JUN, EGR1, ATF3, FOSB, JUNB, DUSP1, EGR2, NR4A1, BTG2, NR4A2.
EGR1 encodes the protein which belongs to the EGR family of C2H2-type zinc-finger proteins. The protein is a nuclear protein that performs transcription. The products of target genes are necessary for differentiation and mitogenesis.9 Xiang Y, et al. find that after undergoing Percutaneous Transluminal Coronary Intervention(PCI) in CHD patients, once EGR1 level significantly decreased once in the early postoperative period, the patient’s coronary may be suspected not having reflow and should be examined timely to improve the effectiveness of therapeutic. 10 EGR1 has been named for the widespread presence and expressing rapidly in human cells. Shajahan-Haq AN, et al. showing that EGR1 has a complex signal pathway, playing a significant role in cell growth and affecting differentiation, proliferation, and inflammatory response.11 Another article, once in the plasma of patients with coronary heart disease, the expression level of EGR1 decreased, it suggests the aggravating of the disease of patients. The level of EGR1can be used to assess the patient’s current status and the progression of disease.12
ATF3 is a gene encoding transcription factors of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family. This gene is induced by a variety of signals, which is related to the happening of the cancer cells and the complex process of the cellular responding to stress. This gene has multiple transcript variants encoding different isoforms. Alternative splicing of this gene may play an important physiological role in regulating target genes. Li YU, et al. shows that upregulation of ATF3 can reduce the heart damage and heart failure induced by hypertension and inhibit cardiac fibroblast cells.13
FOS encodes proteins having been implicated significant relationship with cell proliferation, differentiation, and transformation. The Fos gene family consists of 4 members, including FOS, FOSB, FOSL1, and FOSL2. Dunand-Sauthier I,et al find that c-Fos participates in proliferation, differentiation and apoptosis various cellular processes.6 Several studies have shown that c-Fos decreases proinflammatory cytokine production, and decrease cardiomyocytes death under conditions of hypoxia.7
The protein encoded by BTG2 is a member of the BTG/Tob family which has structurally related proteins have antiproliferative function and is involved in the regulations of the G1/S transition during the cell cycle. BTG2 only affect cytosolic, but not nuclear, RNA levels. Masumura Y, et al shows that under adrenergic stimulation, BTG2 knockdown further enhances cytosolic RNA accumulation in cardiomyocytes. It indicates that BTG2 decrease RNA accumulation to protect cardiomyocytes from hypertrophy.5
The protein encoded by JUNB is a member of the activator protein–1 (AP–1) transcription factor family including Jun (c-Jun, JunB and JunD) and Fos (c-Fos, FosB, Fra–1 and Fra–2).14 JunB combines with the cognitive binding sequence localized in the cis-regulatory region of target genes and participates in cell cycle, proliferation, and apoptosis biological processes. Szremska AP,et al. and Gurzov EN, et al. find that overexpressing JunB can inhibit the proliferation of malignant keratinocytes in mouse,15 and inhibit cell apoptosis in pancreatic beta cells.1618 Also, Chen J, et al. find that JunB can protect heart failure(HF)from inflammatory cardiomyopathy,19 while in zebrafish decreased JunB leads to HF.20
The protein encoded by DUSP1 is an anti-apoptotic phosphatase, and exited in a wide variety of organizations, especially having a high level in the heart.21 One study finds that once I/R injuries happening, decreased DUSP1 can lead to scar expansion, cardiac dysfunction, and cellular death. The absence of DUSP1 triggered fatal mitochondrial fission leading to extensive cell death through increased JNK phosphorylation and the expression of Mff.22
NR4A1 encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. The encoded protein acts as a nuclear transcription factor. When the protein encoded by NR4A1 transferred from nucleus to the mitochondria leads to apoptosis. It has different subtypes of several transcriptional variants which have an efficient function of cardiac repair.23
The protein encoded by BTG2 is affiliated to the BTG/Tob family. This family related proteins have antiproliferative properties. The protein encoded by BTG2 plays an important role in regulating the G1/S transition of the cell cycle. BTG2 can impact the accumulation of cytosolic, but not nuclear, RNA levels. Masumura Y, et al. suggest that though down-regulating the cardiomyocytes accumulation of RNA, BTG2 can attenuate reactive hypertrophy.5
NR4A2, nuclear receptor subfamily 4, group A, member 2, with NR4A1 and NR4A3 composed NR4A orphan nuclear receptor family.24 The NR4A family is the immediate early response transcription factors, which has great relationship with ischemic stroke.25 NR4A2 participates the apoptosis of various cancer cells under stress through different functions.26 In the MI injury mouse, NR4A2 is upregulated. Furthermore, NR4A2 can protect heart from apoptosis and hypertrophy, and also alleviate heart injury.