Qiu Saiwen, Chen Hui, Jiang Qifang
Department of Anesthesiology, Lanxi Traditional Chinese Medicine Hospital, Lanxi, Zhejiang, China.
Department of Anesthesiology, Lanxi People's Hospital, Lanxi, Zhejiang, China.
Front Cardiovasc Med. 2025 Apr 1;12:1515160. doi: 10.3389/fcvm.2025.1515160. eCollection 2025.
This study investigates the preventive benefits of sevoflurane against myocardial ischemia-reperfusion (I/R) injury, focusing on its effect on the modulation of miR-21-5p.
In the clinical study, patients with a history of myocardial ischemia or other conditions requiring surgery were enrolled. Before surgery, the patients were anesthetized with either sevoflurane or propofol. The expression levels of IMA, H-FABP, IL-1β, TNF-α, and IL-6 were also examined. Additionally, the expression of miR-21-5p and its relationships with IMA and H-FABP. A cardiomyocyte hypoxia/reoxygenation (H/R) cell model was created for the tests. The cells were treated with or without sevoflurane and then transfected with inhibitors of miR-21-5p or a negative control (NC). Evaluations were conducted on cell viability, apoptosis ratio, and oxidative stress indicators (MDA, SOD, and ROS). Furthermore, the expression levels of miR-21-5p, apoptotic markers (BCL-2, BAX), myocardial damage markers (IMA, H-FABP), and inflammatory agents (TNF-α, IL-1β, IL-6) were quantified.
In patients with a history of myocardial ischemia, sevoflurane reduced myocardial I/R injury. These patients also showed upregulation of miR-21-5p, which expression positively linked with levels of IMA. Moreover, in H/R treated cardiac cells, sevoflurane markedly reduced the expression of BAX, MDA, ROS, SOD, inflammatory factor and the apoptotic ratio. Nevertheless, inhibition of miR-21-5p abolished these protective effects. Furthermore, in H/R myocardial cells, sevoflurane increased BCL-2 expression and cell survival; these effects were also countered by blocking miR-21-5p.
Mechanistically, we demonstrate for the first time that sevoflurane alleviates myocardial cell injury in myocardial I/R by upregulating miR-21-5p, thereby reducing inflammation, apoptosis, and oxidative stress in myocardial cells. This finding provides a potential therapeutic target for improving myocardial I/R.
本研究调查七氟醚对心肌缺血再灌注（I/R）损伤的预防作用，重点关注其对miR-21-5p调节的影响。
在临床研究中，纳入有心肌缺血病史或其他需要手术的疾病的患者。手术前，患者分别用七氟醚或丙泊酚麻醉。还检测了IMA、H-FABP、IL-1β、TNF-α和IL-6的表达水平。此外，检测miR-21-5p的表达及其与IMA和H-FABP的关系。建立心肌细胞缺氧/复氧（H/R）细胞模型进行试验。细胞用或不用七氟醚处理，然后用miR-21-5p抑制剂或阴性对照（NC）转染。对细胞活力、凋亡率和氧化应激指标（MDA、SOD和ROS）进行评估。此外，对miR-21-5p、凋亡标志物（BCL-2、BAX）、心肌损伤标志物（IMA、H-FABP）和炎症因子（TNF-α、IL-1β、IL-6）的表达水平进行定量。
在有心肌缺血病史的患者中，七氟醚减轻了心肌I/R损伤。这些患者还表现出miR-21-5p上调，其表达与IMA水平呈正相关。此外，在H/R处理的心肌细胞中，七氟醚显著降低了BAX、MDA、ROS、SOD、炎症因子的表达和凋亡率。然而，抑制miR-21-5p消除了这些保护作用。此外，在H/R心肌细胞中，七氟醚增加了BCL-2表达和细胞存活；阻断miR-21-5p也抵消了这些作用。
从机制上讲，我们首次证明七氟醚通过上调miR-21-5p减轻心肌I/R中的心肌细胞损伤，从而减少心肌细胞中的炎症、凋亡和氧化应激。这一发现为改善心肌I/R提供了一个潜在的治疗靶点。
