Therapeutic effect of remimazolam on cerebral ischemia-reperfusion injury rats by regulating the AMP-activated protein kinase/NOD-like receptor protein 3 signaling pathway

doi:10.16098/j.issn.0529-1356.2025.04.007

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Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (4) : 431-437. DOI: 10.16098/j.issn.0529-1356.2025.04.007

Therapeutic effect of remimazolam on cerebral ischemia-reperfusion injury rats by regulating the AMP-activated protein kinase/NOD-like receptor protein 3 signaling pathway

FAN Teng LI Xiao-fang SHEN Dan ZHANG Hong-wei YUE Xiu-qin*

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Abstract

Objective To investigate the effects of remimazolam (REM) on cerebral ischemia-reperfusion injury (CIRI) rats and the AMP-activated protein kinase (AMPK)/NOD-like receptor protein 3 (NLRP3) signaling pathway. Methods One hundred rats were selected to construct the CIRI rat model(Mod) and stochastically separated into a Mod group, low, medium, and high dose remifentanil groups (REM-L, REM-M, REM-H), and high dose remifentanil+pathway inhibitor Compound C group (REM-H+Compound C), with 20 rats in each group. Another 20 healthy rats were included as the control(Ctrl) group. All rats were subjected to neurobehavioral scoring. The water content, infarct area, and oxidative stress indicators of brain tissue were detected. The morphology and apoptosis of brain tissue were observed by HE and TUNEL staining. Western blotting was applied to detect protein expression related to the AMPK/NLRP3 signaling pathway. Results Compared with the Mod group, with the increase of REM dose, the movement disorders in rats were alleviated, the overall structure of brain tissue gradually recovered, pathological damage was reduced, the area of cerebral infarction, brain water content, and apoptosis rate of brain tissue cells decreased, reactive oxygen species(ROS) level, malondialdehyde(MDA) content, and NLRP3 and Caspase-1 protein expression levels decreased, superoxide dismutase the(SOD) content and AMPK protein expression level increased (P<0.05). Compared with the REM-H group, the REM-H+Compound C group showed aggravated motor disorders, and more severe pathological damage to brain tissue, the area of cerebral infarction, cerebral water content and apoptosis rate of brain tissue cells increased, the ROS level, MDA content and the protein expression of NLRP3 and Caspase-1 increased, while the content of SOD and the protein expression decreased (P<0.05). Conclusion Remimazolam can enhance the antioxidant function of the body, reduce brain cell apoptosis, alleviate brain tissue injury, and thus have a certain protective effect on ischemia-reperfusion brain injury in rats, the mechanism of which may be related to the activation of the AMPK/NLRP3 signaling pathway.

Key words

Remimazolam / Ischemia-reperfusion / Brain injury / AMP-activated protein kinase/NOD-like receptor protein 3 signaling pathway / Western blotting / Rat

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FAN Teng LI Xiao-fang SHEN Dan ZHANG Hong-wei YUE Xiu-qin. Therapeutic effect of remimazolam on cerebral ischemia-reperfusion injury rats by regulating the AMP-activated protein kinase/NOD-like receptor protein 3 signaling pathway[J]. Acta Anatomica Sinica. 2025, 56(4): 431-437 https://doi.org/10.16098/j.issn.0529-1356.2025.04.007

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