Mechanisms of Hydromorphone-Mediated Protection Against Myocardial Ischemia-Reperfusion Injury via NLRP3 Inflammasome Inhibition.

IF 4.2 2区医学 Q2 IMMUNOLOGY

Journal of Inflammation Research Pub Date : 2025-05-26 eCollection Date: 2025-01-01 DOI:10.2147/JIR.S509328

Shiyue Zeng, Wei Xu, Fangyuan Ren, Qiangqiang Xiong, Qi Qing, Liu Luo, Xi Song, Yurong Tan, Zhujun Huang, Mingzhi Zheng

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引用次数: 0

Abstract

Background: Myocardial ischaemia/reperfusion, MI/R injury causes significant cardiac damage, leading to disability and mortality. Although hydromorphone attenuates MI/R injury in rat models, its underlying mechanisms remain unclear.

Objective: This study aimed to investigate the protective effects of hydromorphone against MI/R injury and elucidate its mechanisms.

Methods: A rat MIRI model was established by occluding the left coronary artery for 30 minutes followed by reperfusion for 120 minutes. Infarct size and cardiac function were assessed using hematoxylin-eosin, HE and Masson's staining. An in vitro model was established using H9C2 cells subjected to hypoxia/reoxygenation, and levels of cellular pyroptosis and pyroptosis-related proteins were quantified.

Results: Hydromorphone significantly improved cardiac function in MIRI rats. Pre- and post-treatment with hydromorphone significantly improved cardiomyocyte morphology in MIRI rats. In addition, compared with the model group (IR), the hydromorphone-treated groups (HH+IR, IR+HH) significantly reduced the rna expression of NLRP3, ASC, caspase-1, IL-1β, and IL-18, as well as the protein levels of IL-1β, IL-18. In addition, transmission electron microscopy showed that hydromorphone attenuated CoCl2-induced cardiomyocyte injury.

Conclusion: Pre- or post-treatment with hydromorphone exerts protective effects against MIRI by suppressing NLRP3 inflammasomes, potentially providing a theoretical basis for its use as a therapeutic agent in MIRI patients.

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氢吗啡酮通过抑制NLRP3炎性体对心肌缺血再灌注损伤的保护机制

背景：心肌缺血/再灌注，MI/R损伤可导致严重的心脏损伤，导致残疾和死亡。虽然氢吗啡酮在大鼠模型中减轻心肌梗死/再灌注损伤，但其潜在机制尚不清楚。目的：研究氢吗啡酮对心肌梗死/心肌梗死的保护作用，并探讨其机制。方法：采用左冠状动脉闭塞30 min，再灌注120 min的方法建立大鼠MIRI模型。采用苏木精-伊红染色、HE染色、Masson染色评估梗死面积和心功能。采用缺氧/复氧H9C2细胞建立体外模型，定量测定细胞焦亡及焦亡相关蛋白水平。结果：氢吗啡酮明显改善MIRI大鼠心功能。氢吗啡酮治疗前后可显著改善MIRI大鼠心肌细胞形态。此外，与模型组（IR）相比，氢吗啡酮处理组（HH+IR、IR+HH）显著降低NLRP3、ASC、caspase-1、IL-1β、IL-18的rna表达以及IL-1β、IL-18的蛋白水平。此外，透射电镜显示氢吗啡酮可减轻cocl2诱导的心肌细胞损伤。结论：氢吗啡酮治疗前后通过抑制NLRP3炎性小体对MIRI具有保护作用，可能为其作为MIRI患者的治疗剂提供理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Inflammation Research Immunology and Microbiology-Immunology

CiteScore

6.10

自引率

2.20%

发文量

658

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.