He Tianping, Huang Jianfeng, Peng Bo, Wang Mianhui, Shui Qiuhao, Cai Liang
Department of Anesthesiology, Luxian People's Hospital Luzhou 646100, Sichuan, China.
Department of Anesthesiology, The People's Hospital of Leshan Leshan 614013, Sichuan, China.
Am J Transl Res. 2024 Mar 15;16(3):755-767. doi: 10.62347/MTAY7931. eCollection 2024.
To identify hub genes and biological processes of propofol-induced neurotoxicity and promote the development of pediatric anesthesiology.
We downloaded the GSE106799 dataset from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened, then Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment analyses were performed on all DEGs. We identified potential ferroptosis genes in the pathogenesis of propofol-induced neurotoxicity. A key module was obtained after performing weighted gene co-expression network analysis (WGCNA) on the GSE106799 dataset. Hub genes were identified after the least absolute shrinkage and selection operator (LASSO) regression analysis of the intersection of DEGs and genes from the key module. We established a competing endogenous RNA network and predicted potential drugs according to the hub genes. Total RNA and proteins were extracted for real-time quantitative polymerase chain reaction and Western blotting, respectively.
A total of 112 DEGs, including 76 upregulated and 36 downregulated ones were screened out. Propofol-induced neurotoxicity involved processes such as nervous system development, activation of JAK/STAT and MAPK signaling pathways, vascular regeneration, and oxidative stress. The results of WGCNA suggested that the tan module was the most strongly associated with propofol-induced neurotoxicity. We identified 4 hub genes () after LASSO regression analysis. Animal experiments demonstrated that propofol caused overexpression of the protein levels of and inflammatory factors in the brain, as well as the mRNA levels of and . Propofol inhibited expression of at mRNA and protein levels.
Previous studies have demonstrated that and play a role in intellectual development, neuroinflammation and neuronal differentiation. These hub genes may help us to find new preventive and therapeutic targets for propofol-induced neurotoxicity.
鉴定丙泊酚诱导神经毒性的关键基因和生物学过程，促进小儿麻醉学的发展。
从基因表达综合数据库下载GSE106799数据集。筛选差异表达基因（DEGs），然后对所有DEGs进行京都基因与基因组百科全书、基因本体论和基因集富集分析。我们在丙泊酚诱导神经毒性的发病机制中鉴定了潜在的铁死亡基因。对GSE106799数据集进行加权基因共表达网络分析（WGCNA）后获得一个关键模块。对DEGs与关键模块中的基因的交集进行最小绝对收缩和选择算子（LASSO）回归分析后鉴定关键基因。我们建立了一个竞争性内源性RNA网络，并根据关键基因预测潜在药物。分别提取总RNA和蛋白质用于实时定量聚合酶链反应和蛋白质印迹法。
共筛选出112个DEGs，其中76个上调，36个下调。丙泊酚诱导的神经毒性涉及神经系统发育、JAK/STAT和MAPK信号通路激活、血管再生和氧化应激等过程。WGCNA结果表明，棕色模块与丙泊酚诱导的神经毒性相关性最强。LASSO回归分析后我们鉴定了4个关键基因。动物实验表明，丙泊酚导致大脑中某些蛋白水平和炎症因子的过表达，以及某些基因的mRNA水平升高。丙泊酚在mRNA和蛋白质水平上抑制某基因的表达。
先前的研究表明某些基因在智力发育、神经炎症和神经元分化中起作用。这些关键基因可能有助于我们找到丙泊酚诱导神经毒性的新的预防和治疗靶点。
