Zhang Yuhu, Li Xinjian, Sun Tingru
Department of Anesthesiology Medicine, The First Hospital of Zibo, Zibo, China.
Department of Cardiovascular Medicine, The First Hospital of Zibo, Zibo, China.
Front Surg. 2025 Jul 9;12:1515732. doi: 10.3389/fsurg.2025.1515732. eCollection 2025.
Anesthetics have been reported to play a protective role in the heart during surgery. This study aimed to identify mitochondrial-related genes (Mito-RGs) involved in sevoflurane- and propofol-induced anesthesia in patients undergoing off-pump coronary artery bypass grafting (OPCABG) surgery.
The GSE4386 dataset, which contains atrial samples obtained from patients receiving sevoflurane or propofol during OPCABG, was downloaded from GEO database for differential expression analysis and immune cell infiltration analysis between the pre-operative and post-surgery groups. Furthermore, to model the ischemia-reperfusion injury encountered during cardiac surgery, we established an hypoxia/reoxygenation (H/R) model and investigated the effects of sevoflurane and propofol on the expression of hub genes in cardiomyocytes subjected to H/R injury.
In this study, we identified a total of 11 common Mito-RGs that were influenced by sevoflurane and propofol during OPCABG. Furthermore, a PPI network of these genes was constructed using STRING, followed by the application of the MCODE and cytoHubba plug-ins to further identify hub genes within the network. Our analysis revealed that MCL1, RGS2, PPP1R15A, and MAFF may be the hub Mito-RGs associated with anesthetics. In the post-surgery group, the levels of these genes were negatively correlated with pro-inflammatory M1 macrophages. Notably, compared to pre-OPCABG levels, both sevoflurane and propofol significantly upregulated the expressions of these four hub genes in atrial samples following OPCABG. Furthermore, RT-qPCR and western blot analyses validated that both sevoflurane and propofol can upregulate the expression of Maff, Ppp1r15a, Rgs2, and Mcl1 in H9C2 cardiomyocytes following H/R injury.
Collectively, these four genes may be linked to the potential cardioprotective effects of anesthetics during OPCABG, which could facilitate further research into the underlying mechanisms and contribute to the development of a more comprehensive and effective anesthesia protocol.
据报道，麻醉剂在手术过程中对心脏具有保护作用。本研究旨在确定非体外循环冠状动脉搭桥术（OPCABG）患者中，与七氟醚和丙泊酚诱导的麻醉相关的线粒体相关基因（Mito-RGs）。
从GEO数据库下载GSE4386数据集，该数据集包含OPCABG期间接受七氟醚或丙泊酚的患者的心房样本，用于术前和术后组之间的差异表达分析和免疫细胞浸润分析。此外，为了模拟心脏手术中遇到的缺血再灌注损伤，我们建立了缺氧/复氧（H/R）模型，并研究了七氟醚和丙泊酚对H/R损伤的心肌细胞中枢纽基因表达的影响。
在本研究中，我们共鉴定出11个在OPCABG期间受七氟醚和丙泊酚影响的常见Mito-RGs。此外，使用STRING构建了这些基因的蛋白质-蛋白质相互作用（PPI）网络，随后应用MCODE和cytoHubba插件进一步鉴定网络中的枢纽基因。我们的分析表明，MCL1、RGS2、PPP1R15A和MAFF可能是与麻醉剂相关的枢纽Mito-RGs。在术后组中，这些基因的水平与促炎性M1巨噬细胞呈负相关。值得注意的是，与OPCABG术前水平相比，七氟醚和丙泊酚均显著上调了OPCABG术后心房样本中这四个枢纽基因的表达。此外，逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹分析证实，七氟醚和丙泊酚均可在H/R损伤后上调H9C2心肌细胞中Maff、Ppp1r15a、Rgs2和Mcl1的表达。
总的来说，这四个基因可能与OPCABG期间麻醉剂的潜在心脏保护作用有关，这有助于进一步研究其潜在机制，并为制定更全面有效的麻醉方案做出贡献。
