实用临床医药杂志2025，Vol.29Issue(4)：16-22,7.DOI:10.7619/jcmp.20245427
瑞马唑仑对大鼠视网膜缺血再灌注损伤的作用及机制研究
Effect and mechanism of remimazolam on retinal ischemia-reperfusion injury in rats
摘要
Abstract
Objective To investigate the effect of remimazolam(Rem)on retinal ischemia-reper-fusion 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 in-traocular 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.En-zyme-linked immunosorbent assay(ELISA)was performed to detect the expression levels of interleu-kin-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 dis-mutase(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 ret-inal cell apoptosis rate,serum levels of IL-1 β,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-1 β,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.Conclusion Rem can inhibit the occurrence of RIRI in rats,and its mecha-nism of action may be related to the regulation of the HMGB1/RAGE/NF-κB signaling pathway.关键词
视网膜缺血再灌注损伤/瑞马唑仑/高迁移率族蛋白B1/晚期糖基化终末产物受体/核转录因子-κB/信号通路Key words
retinal ischemia-reperfusion injury/remimazolam/high-mobility group box 1/receptor for advanced glycation end products/nuclear factor-κB/signaling pathway分类
医药卫生引用本文复制引用
武苗,陈星,牛静芬,王军..瑞马唑仑对大鼠视网膜缺血再灌注损伤的作用及机制研究[J].实用临床医药杂志,2025,29(4):16-22,7.基金项目
山西省卫生健康委科研课题(2020109) （2020109）
