Remimazolam alleviates myocardial ischemia/reperfusion injury and inflammation via inhibition of the NLRP3/IL‑1&beta; pathway in mice

Liu,Xueru; Shui,Guojing; Wang,Yan; Chen,Tangting; Zhang,Peng; Liu,Li; Li,Chunhong; Li,Tao; Wang,Xiaobin

doi:10.3892/ijmm.2025.5498

Remimazolam alleviates myocardial ischemia/reperfusion injury and inflammation via inhibition of the NLRP3/IL‑1β pathway in mice

Authors:
- Xueru Liu
- Guojing Shui
- Yan Wang
- Tangting Chen
- Peng Zhang
- Li Liu
- Chunhong Li
- Tao Li
- Xiaobin Wang
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Affiliations: Department of Anesthesiology, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Key Laboratory of Medical Electrophysiology of the Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: January 30, 2025 https://doi.org/10.3892/ijmm.2025.5498
Article Number: 57
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Remimazolam (Rema) is a novel anesthetic that is widely used in anesthesia and sedation in critically ill patients. Notably, Rema exerts effects in patients through activation of the γ‑aminobutyric acid (GABA) receptor. GABA may alleviate myocardial ischemia/reperfusion (I/R) injury; however, the impact of Rema and underlying molecular mechanism in myocardial I/R injury remain to be fully understood. Therefore, the present study aimed to investigate the effects of Rema on cardiac I/R injury and to determine the underlying mechanisms. An acute myocardial I/R model was established by ligating the left anterior descending artery in adult male C57BL/6 mice (8‑10 weeks). Cultured Raw264.7 cells treated with lipopolysaccharide (LPS) were also used to investigate the effect of Rema on macrophages. The results of the present study revealed that Rema improved I/R‑induced cardiac dysfunction by increasing the ejection fraction value and reducing the myocardial infarction area. In addition, Rema also alleviated I/R‑induced cardiac inflammatory cell infiltration based on H&E and immunofluorescence staining. Transmission electron microscopy and ROS measurements showed that Rema improved I/R‑induced mitochondrial structural disruption and oxidative stress in cardiomyocytes. Transcriptomics analysis and reverse transcription‑quantitative PCR revealed that Rema alleviated I/R‑induced release of inflammatory factors and cytokines by inhibiting the expression of IL‑1β, IL‑6, C‑C chemokine receptor 2 and C‑X‑C motif chemokine ligand 5. Rema also inhibited I/R‑induced CD68+ cell proliferation, IL‑1β release, and NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) and IL‑1β expression. The results of in vitro assays revealed that Rema inhibited LPS‑induced increases in IL‑1β, IL‑6 and TNF‑α expression and release in cultured RAW264.7 macrophages. In conclusion, the present study revealed that Rema may alleviate I/R‑induced cardiac dysfunction and myocardial injury by inhibiting oxidative stress and inflammatory responses via the NLRP3/IL‑1β pathway.

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