Feng Mingjing, Zheng Lingling, Chen Baozeng, Shi Huijian
Department of Anesthesiology, The Second People's Hospital of Liaocheng, Liaocheng, Shandong, China.
Department of Cardiology, Shengli Oilfield Central Hospital, Dongying, Shandong, China.
Anal Cell Pathol (Amst). 2025 Aug 24;2025:7119597. doi: 10.1155/ancp/7119597. eCollection 2025.
The purpose of this study was to investigate the impact of sevoflurane (SEV) on cardiomyocyte (CM) pyroptosis following myocardial ischemia (MI). Reverse validation was performed by pharmacologically activating NLRP3 with monosodium urate (MSU) to confirm that SEV's cardioprotective effects were specifically mediated through the NLRP3 inflammasome pathway. Sprague Dawley rats were randomly assigned to sham (sham), model (conventional anesthesia + MI-reperfusion [MIR] injury modeling), SEV (SEV inhalation anesthesia + MIR injury modeling), and SEV + NLRP3 (SEV inhalation anesthesia + MIR injury modeling + NLRP3) groups. The myocardial area at risk (MAAR) and the myocardial infarct size (MIS) were evaluated in each experimental group, and cardiac tissue was examined using hematoxylin-eosin (H&E), Masson trichrome, and TUNEL staining. The concentrations of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), oxidative stress (OS), and pyroptosis-associated proteins and various inflammatory markers in the serum and cardiac tissue were quantified. Results showed that compared to the sham group, both model and SEV groups exhibited a significant increase in MAAR and MIS, accompanied by severe histopathological damage and noticeable OS ( < 0.05). Elevated levels of inflammatory factors, enhanced CM apoptosis, and increased expression of pyroptosis-associated proteins were also observed in these groups. Notably, the SEV intervention in the SEV group demonstrated evident mitigation of heart injury, reduced MAAR and MIS, diminished CM apoptosis and inflammatory factors, and suppressed pyroptosis-associated proteins. Additionally, we observed that NLRP3 activation significantly diminished the protective effects of SEV on MIR rats. This study uncovers a novel mechanism through which SEV suppresses CM pyroptosis by inhibiting NLRP3, as confirmed by pharmacological activation of NLRP3. This was evidenced by worsened histopathological damage, increased CM apoptosis, and higher levels of inflammatory factors, cardiac injury markers, and pyroptosis-associated proteins. Overall, SEV inhibits CM pyroptosis and mitigates OS and inflammation through the NLRP3 inflammasome.
本研究旨在探讨七氟醚（SEV）对心肌缺血（MI）后心肌细胞（CM）焦亡的影响。通过用尿酸钠（MSU）药理学激活NLRP3进行反向验证，以确认SEV的心脏保护作用是通过NLRP3炎性小体途径特异性介导的。将Sprague Dawley大鼠随机分为假手术组（sham）、模型组（传统麻醉+心肌缺血再灌注[MIR]损伤建模）、SEV组（SEV吸入麻醉+MIR损伤建模）和SEV+NLRP3组（SEV吸入麻醉+MIR损伤建模+NLRP3）。评估每个实验组的心肌危险区面积（MAAR）和心肌梗死面积（MIS），并使用苏木精-伊红（H&E）、Masson三色染色和TUNEL染色检查心脏组织。定量测定血清和心脏组织中肌酸激酶-MB（CK-MB）、心肌肌钙蛋白I（cTnI）、氧化应激（OS）、焦亡相关蛋白和各种炎症标志物的浓度。结果显示，与假手术组相比，模型组和SEV组的MAAR和MIS均显著增加，伴有严重的组织病理学损伤和明显的OS（<0.05）。在这些组中还观察到炎症因子水平升高、CM凋亡增强以及焦亡相关蛋白表达增加。值得注意的是，SEV组中的SEV干预显示出心脏损伤明显减轻，MAAR和MIS降低，CM凋亡和炎症因子减少，焦亡相关蛋白受到抑制。此外，我们观察到NLRP3激活显著减弱了SEV对MIR大鼠的保护作用。本研究揭示了一种新机制，即SEV通过抑制NLRP3来抑制CM焦亡，这通过NLRP3的药理学激活得到证实。组织病理学损伤加重、CM凋亡增加以及炎症因子、心脏损伤标志物和焦亡相关蛋白水平升高证明了这一点。总体而言，SEV通过NLRP3炎性小体抑制CM焦亡并减轻OS和炎症。
