Effect and mechanism of remimazolam on retinal ischemia-reperfusion injury in rats

WU Miao; CHEN Xing; NIU Jingfen; WANG Jun

doi:10.7619/jcmp.20245427

Journal of Clinical Medicine in Practice > 2025 > 29(4): 16-22. > DOI: 10.7619/jcmp.20245427

WU Miao, CHEN Xing, NIU Jingfen, WANG Jun. Effect and mechanism of remimazolam on retinal ischemia-reperfusion injury in rats[J]. Journal of Clinical Medicine in Practice, 2025, 29(4): 16-22. DOI: 10.7619/jcmp.20245427

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Effect and mechanism of remimazolam on retinal ischemia-reperfusion injury in rats

1.
Department of Anesthesiology, Taiyuan Hospital of Peking University First Hospital, Taiyuan Municipal Center Hospital, Taiyuan, Shanxi, 030009
2.
Department of Ultrasonography, Taiyuan Hospital of Peking University First Hospital, Taiyuan Municipal Center Hospital, Taiyuan, Shanxi, 030009

More Information

Received Date: November 07, 2024
Revised Date: December 09, 2024
Available Online: December 12, 2024

Graphical Abstract

Abstract

Abstract

Objective
To investigate the effect of remimazolam (Rem) on retinal ischemia-reperfusion injury (RIRI) in rats and its regulatory mechanism on the high-mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE)/nuclear factor-κB (NF-κB) signaling pathway.
Methods
Rats were randomly divided into Sham group, Model group, Rem-L group (low-dose Rem), Rem-M group (medium-dose Rem), Rem-H group (high-dose Rem), and high-dose Rem plus HMGB1 activator dexamethasone (DEX) group (Rem-H+DEX group), with 15 rats in each group. Except for the Sham group, RIRI model was established in the other groups by increasing intraocular pressure. Hematoxylin and eosin (HE) staining was used to observe the changes in retinal tissue structure in each group. The TUNEL method was used to detect retinal tissue apoptosis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the serum of rats in each group. Kits were used to detect the levels of oxidative stress indicators, including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA). Western blot was used to detect the expression levels of hypoxia-related factors [hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF)] and HMGB1/RAGE/NF-κB signaling pathway-related proteins in retinal tissue.
Results
Compared with the Sham group, the Model group showed severe retinal edema, a significant decrease in the number of ganglion cells, vacuolar changes in cells with disordered arrangement, and widened cell gaps. With increasing doses of Rem, the degree of retinal edema gradually decreased, the number of ganglion cells increased, and their arrangement became more orderly in RIRI rats. Compared with the Sham group, the Model group exhibited increased retinal cell apoptosis rate, serum levels of IL-1β, IL-6, and TNF-α and increased expression levels of MDA, HMGB1, RAGE, NF-κB, HIF-1α and VEGF in retinal tissue, while the expression levels of SOD and GSH-PX decreased (P < 0.05). Compared with the Model group, the Rem-L, Rem-M, and Rem-H groups showed dose-dependent decreases in retinal cell apoptosis rate, serum levels of IL-1β, IL-6, and TNF-α, and expression levels of MDA, HMGB1, RAGE, NF-κB, HIF-1α and VEGF in retinal tissue, with dose-dependent increases in the expression levels of SOD and GSH-PX (P < 0.05). Compared with the Rem-H group, the Rem-H+DEX group showed reversed trends in the above indicators.
Conclusions
Rem can inhibit the occurrence of RIRI in rats, and its mechanism of action may be related to the regulation of the HMGB1/RAGE/NF-κB signaling pathway.

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References (23)

References

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Effect and mechanism of remimazolam on retinal ischemia-reperfusion injury in rats