Xu Guohao, Sun Xiaotong, An Jianxiong, Sun Fan, Zhang Chengming, Williams John P
Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology, Shandong Second Medical University, Weifang, Shandong, 261000, China; Institute for Lnnovation Diagnosis & Treatment in Anesthesiology, Shandong Second Medical University, Weifang, Shandong Province, China; Pain and Sleep Medicine Center, Rapid Anti-depression Center, The Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong Province, China.
Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology, Shandong Second Medical University, Weifang, Shandong, 261000, China.
Eur J Pharmacol. 2025 Jun 15;997:177631. doi: 10.1016/j.ejphar.2025.177631. Epub 2025 Apr 15.
Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide. Myocardial ischemia/reperfusion injury (MIRI) is the primary cause of myocardial injury triggered by post-myocardial infarction reperfusion therapy. Its pathogenesis involves Ca overload, the production of large amounts of oxygen-free radicals, inflammation, and cell necrosis. Growing evidence suggests that the NLRP3 inflammasome significantly contributes to the sterile inflammatory response and pyroptosis in MIRI, linking damage sensing to the initiation and amplification of the inflammatory response. Reportedly, ozone exerts anti-inflammatory and anti-infection effects by activating the antioxidant system. Additional evidence suggests that ozone inhibits NLRP3 inflammasome expression to relieve ischemic injury. In this study, we aimed to explore whether pretreating the myocardium with ozone protects it from MIRI by inhibiting the NLRP3 inflammasome. Rats were subjected to rectal infusion of ozone for 5 consecutive days, followed by ligation of the left anterior descending coronary artery for 30 min and reperfusion for 120 min to induce MIRI. Experimental results were obtained using echocardiography, triphenyltetrazolium chloride and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assay. The results showed that ozone significantly improved the diastolic function of the heart, reduced the area of myocardial infarction, and decreased the expression levels of NLRP3, pro-caspase-1, ASC, and the secretion of caspase-1, interleukin (IL)-1β, and IL-18. In summary, these findings reveal that ozone pretreatment can alleviate the damage that occurs during MIRI by inhibiting the NLRP3 Inflammasome.
缺血性心脏病（IHD）是全球发病和死亡的主要原因。心肌缺血/再灌注损伤（MIRI）是心肌梗死后再灌注治疗引发心肌损伤的主要原因。其发病机制涉及钙超载、大量氧自由基的产生、炎症和细胞坏死。越来越多的证据表明，NLRP3炎性小体在MIRI的无菌性炎症反应和细胞焦亡中起重要作用，将损伤感知与炎症反应的启动和放大联系起来。据报道，臭氧通过激活抗氧化系统发挥抗炎和抗感染作用。更多证据表明，臭氧抑制NLRP3炎性小体表达以减轻缺血性损伤。在本研究中，我们旨在探讨用臭氧预处理心肌是否通过抑制NLRP3炎性小体来保护其免受MIRI损伤。大鼠连续5天接受直肠灌注臭氧，然后结扎左冠状动脉前降支30分钟并再灌注120分钟以诱导MIRI。使用超声心动图、氯化三苯基四氮唑和苏木精-伊红染色、蛋白质印迹法和酶联免疫吸附测定获得实验结果。结果表明，臭氧显著改善心脏舒张功能，减少心肌梗死面积，并降低NLRP3、前半胱天冬酶-1、ASC的表达水平以及半胱天冬酶-1、白细胞介素（IL）-1β和IL-18的分泌。总之，这些发现揭示了臭氧预处理可以通过抑制NLRP3炎性小体来减轻MIRI期间发生的损伤。
