Cannabinoid Receptor-2 agonist AM1241 Attenuates Myocardial Ischemia-Reperfusion-Induced Oxidative Stress in Rats via Nrf2/HO-1 Pathway.

IF 2.9 3区医学 Q1 MEDICINE, GENERAL & INTERNAL Medical Principles and Practice Pub Date : 2024-01-01 Epub Date: 2024-08-12 DOI:10.1159/000540751

Mingxiao Zhang, Qingxin Tian, Jianlong Liu

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Abstract

Objective: The cannabinoid receptor-2 agonist AM1241 exhibits notable cardioprotective effects against myocardial infarction, positioning it as a promising therapeutic candidate for cardiovascular disease. This study explores AM1241's protective role in myocardial ischemia-reperfusion (IR) injury and its association with the Nrf2/HO-1 pathway.

Methods: In an established Sprague-Dawley rat IR model, AM1241's impact on cardiac injury was assessed through echocardiography, 2,3,5-triphenyl tetrazolium chloride staining, and histological analysis. H9c2 cells underwent hypoxia-reoxygenation, with AM1241's influence on cell viability determined by the CCK-8 assay. Reactive oxygen species (ROS) production was measured using the DCFH-DA assay, and Nrf2 and HO-1 protein expressions were evaluated through immunofluorescence and Western blot.

Results: Myocardial ischemia-reperfusion injury (MIRI) increased infarct size, inflammatory cell presence, oxidative and nitrosative stress, impaired cardiac function, and elevated apoptosis rates. AM1241 mitigated these effects, enhancing cell viability, reducing ROS production, and upregulating Nrf2 and HO-1 expression. The antioxidant effect of AM1241 was inhibited by ML385 intervention.

Conclusions: AM1241 attenuates oxidative stress, alleviates MIRI, and activates the Nrf2/HO-1 signaling pathway, underscoring its potential as a therapeutic strategy for MIRI.

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大麻素受体-2激动剂AM1241通过Nrf2/HO-1途径减轻大鼠心肌缺血再灌注诱导的氧化应激反应

目的：大麻素受体-2激动剂AM1241对心肌梗死具有显著的心脏保护作用，因此有望成为心血管疾病的候选治疗药物。本研究探讨了 AM1241 在心肌缺血再灌注（IR）损伤中的保护作用及其与 Nrf2/HO-1 通路的关联：在已建立的 SD 大鼠 IR 模型中，通过超声心动图、2,3,5-三苯基氯化四氮唑染色和组织学分析评估 AM1241 对心脏损伤的影响。对 H9c2 细胞进行缺氧-复氧，通过 CCK-8 检测法确定 AM1241 对细胞活力的影响。用 DCFH-DA 法检测活性氧（ROS）的产生，并通过免疫荧光和 Western 印迹评估 Nrf2 和 HO-1 蛋白的表达：结果：心肌缺血再灌注损伤（MIRI）增加了梗死面积、炎症细胞的存在、氧化应激和亚硝酸应激、心功能受损以及细胞凋亡率升高。AM1241 可减轻这些影响，提高细胞活力，减少 ROS 的产生，上调 Nrf2 和 HO-1 的表达。ML385的干预抑制了AM1241的抗氧化作用：结论：AM1241可减轻氧化应激，缓解MIRI，并激活Nrf2/HO-1信号通路，因此有望成为心肌缺血再灌注损伤的一种治疗策略。

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来源期刊

Medical Principles and Practice 医学-医学：内科

CiteScore

6.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Medical Principles and Practice'', as the journal of the Health Sciences Centre, Kuwait University, aims to be a publication of international repute that will be a medium for dissemination and exchange of scientific knowledge in the health sciences.