Gu Qian-Lin, Jiang Peng, Ruan Hui-Fen, Tang Hao, Liang Yang-Bing, Ma Zhong-Fu, Zhan Hong
Emergency Department, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, China.
Huangpu District Emergency Department, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, China.
World J Emerg Med. 2022;13(2):106-113. doi: 10.5847/wjem.j.1920-8642.2022.021.
We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury (MIRI) in patients with acute ST-elevation myocardial infarction (STEMI) using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.
The mononuclear cells were separated by ficoll centrifugation, and plasma total antioxidant capacity (T-AOC) was determined by the ferric reducing ability of plasma (FRAP) assay. The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, gene ontology (GO) enrichment analysis was performed on DAVID website to analyze the potential mechanism further.
The total numbers of white blood cells (WBC) and neutrophils (N) in the peripheral blood of STEMI patients (the AMI group) were significantly higher than those in the control group (WBC: 11.67±4.85 ×10/L vs. 6.41±0.72 ×10/L, <0.05; N: 9.27±4.75 ×10/L vs. 3.89±0.81 ×10/L, <0.05), and WBCs were significantly associated with creatine kinase-myocardial band (CK-MB) on the first day (=8.945+0.018, <0.05). In addition, the T-AOC was significantly lower in the AMI group comparing to the control group (12.80±1.79 U/mL vs. 20.48±2.55 U/mL, <0.05). According to the gene analysis, eight up-regulated differentially expressed genes (DEGs) included , , , , , , , and . Four down-regulated DEGs contained , , , and . and were detected by polymerase chain reaction (PCR) to verify the expression at different time points, and the results showed that was up-regulated and was down-regulated as the total expression. GO and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response (UPR) and apoptosis.
WBCs, especially neutrophils, were the critical cells that mediating reperfusion injury. MIRI was regulated by various genes, including oxidative metabolic stress, heat shock, DNA damage and repair, and apoptosis-related genes. The underlying pathway may be associated with UPR and apoptosis, which may be the novel therapeutic target.
我们旨在采用应激和毒性通路基因芯片技术研究急性ST段抬高型心肌梗死（STEMI）患者心肌缺血/再灌注损伤（MIRI）的基因表达情况，并试图确定其潜在机制。
采用菲可离心法分离单核细胞，通过血浆铁还原能力（FRAP）测定法测定血浆总抗氧化能力（T-AOC）。通过寡核苷酸基因芯片和定量实时聚合酶链反应（qRT-PCR）测定并验证毒性氧化应激基因的表达。此外，在DAVID网站上进行基因本体论（GO）富集分析以进一步分析潜在机制。
STEMI患者（急性心肌梗死组）外周血白细胞（WBC）和中性粒细胞（N）总数显著高于对照组（WBC：11.67±4.85×10⁹/L对6.41±0.72×10⁹/L，P<0.05；N：9.27±4.75×10⁹/L对3.89±0.81×10⁹/L，P<0.05），且第1天时WBC与肌酸激酶同工酶（CK-MB）显著相关（r=8.945+0.018，P<0.05）。此外，与对照组相比，急性心肌梗死组的T-AOC显著降低（12.80±1.79 U/mL对20.48±2.55 U/mL，P<0.05）。根据基因分析，8个上调的差异表达基因（DEG）包括……、……、……、……、……、……、……和……。4个下调的DEG包含……、……、……和……。通过聚合酶链反应（PCR）检测……和……在不同时间点的表达以进行验证，结果显示……总体表达上调而……下调。GO和京都基因与基因组百科全书（KEGG）富集分析表明，氧化应激基因通过未折叠蛋白反应（UPR）和凋亡等多种途径介导MIRI。
WBC，尤其是中性粒细胞，是介导再灌注损伤的关键细胞。MIRI受多种基因调控，包括氧化代谢应激、热休克、DNA损伤与修复以及凋亡相关基因。潜在途径可能与UPR和凋亡相关，这可能是新的治疗靶点。
