Esketamine alleviated cardiomyocyte ferroptosis induced by oxygen-glucose deprivation/reoxygenation (OGD/R) via cyclic GMP-AMP synthase interactor.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2025-04-01 Epub Date: 2025-02-08 DOI:10.1007/s10616-025-00723-9

Jianjun Ouyang, Weiqiang Xiao, Di Wu, Manyun Bai, Qian Zhao, Yufang Li

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引用次数: 0

Abstract

Background: The use of tourniquets (TQ) during the total knee arthroplasty (TKA) induced ischemia-reperfusion (I/R) injury in the limb, resulting in the release of inflammatory cytokines and reactive oxygen species (ROS), therefore leading to myocardial damage. This study aimed to investigate the effects and molecular mechanism of Esketamine on myocardial injury (MI) caused by TQ-induced I/R injury.

Methods: A randomized numerical table method was used to divide 23 patients into the C group (11 cases, ACB + conventional anesthesia) and M group (12 cases, ACB + conventional anesthesia + 0.5 mg/kg Esketamine). The levels of lactate dehydrogenase (LDH), Malondialdehyde (MDA), Fe²⁺, Glutathione Peroxidase (GSH-Px), glutathione (GSH), IL-6, TNF-α, Creatine Kinase (CK) and CreatineKinase-MB (CKMB) were determined by reagent kits. The expression of CGAMP interaction factor (STING), Glutathione Peroxidase 4 (GPX4), and Ferritin Heavy Chain 1 (FTH1) was examined by Western blot. The ROS level was tested by flow cytometry. The expression of STING was validated by immunofluorescence.

Results: Compared with the C group, the levels of GSH-Px and GSH were increased while the levels of IL-6, TNF-α, MDA, Fe²⁺, CK, CKMB, and LDH were decreased in the M group. Furthermore, esketamine relieved the OGD/R-induced increase of MDA, Fe²⁺, and ROS and the decrease of GSH-Px, GSH, GPX4, and FTH1, which were reversed by STING overexpression.

Conclusion: Esketamine alleviated cardiomyocyte ferroptosis via STING, which might be the molecular mechanism of Esketamine to ameliorate the MI caused by TQ-induced I/R injury.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-025-00723-9.

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艾氯胺酮通过环GMP-AMP合成酶相互作用减轻氧-葡萄糖剥夺/再氧化（OGD/R）诱导的心肌细胞凋亡。

背景：在全膝关节置换术（TKA）中使用止血带（TQ）引起肢体缺血再灌注（I/R）损伤，导致炎症因子和活性氧（ROS）的释放，从而导致心肌损伤。本研究旨在探讨艾氯胺酮对tq诱导I/R损伤心肌损伤（MI）的影响及其分子机制。方法：采用随机数字表法将23例患者分为C组（11例，ACB +常规麻醉）和M组（12例，ACB +常规麻醉+ 0.5 mg/kg艾氯胺酮）。采用试剂盒检测乳酸脱氢酶（LDH）、丙二醛（MDA）、Fe2+、谷胱甘肽过氧化物酶（GSH- px）、谷胱甘肽（GSH）、IL-6、TNF-α、肌酸激酶（CK）、肌酸激酶- mb （CKMB）水平。Western blot检测CGAMP相互作用因子（STING）、谷胱甘肽过氧化物酶4 （GPX4）、铁蛋白重链1 （FTH1）的表达。流式细胞术检测ROS水平。免疫荧光法验证STING的表达。结果：与C组比较，M组GSH- px、GSH水平升高，IL-6、TNF-α、MDA、Fe2+、CK、CKMB、LDH水平降低。此外，艾氯胺酮还能缓解OGD/ r诱导的MDA、Fe2+和ROS的升高，以及GSH- px、GSH、GPX4和FTH1的降低，而这一现象被STING过表达逆转。结论：艾氯胺酮通过STING减轻心肌细胞铁下垂，这可能是艾氯胺酮改善tq诱导I/R损伤致心肌梗死的分子机制。补充信息：在线版本包含补充资料，可在10.1007/s10616-025-00723-9获得。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.