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

作　　者：武苗 陈星 牛静芬 王军[2] WU Miao;CHEN Xing;NIU Jingfen;WANG Jun(Department of Anesthesiology,Taiyuan Hospital of Peking University First Hospital,Taiyuan Municipal Center Hospital,Taiyuan,Shanxi,030009;Department of Ultrasonography,Taiyuan Hospital of Peking University First Hospital,Taiyuan Municipal Center Hospital,Taiyuan,Shanxi,030009)

机构地区：[1]北京大学第一医院太原医院/太原市中心医院麻醉科,山西太原030009 [2]北京大学第一医院太原医院/太原市中心医院超声科,山西太原030009

出　　处：《实用临床医药杂志》2025年第4期16-22,共7页Journal of Clinical Medicine in Practice

基　　金：山西省卫生健康委科研课题(2020109)。

摘　　要：目的探讨瑞马唑仑(Rem)对大鼠视网膜缺血再灌注损伤(RIRI)的作用及其对高迁移率族蛋白B1(HMGB1)/晚期糖基化终末产物受体(RAGE)/核转录因子-κB(NF-κB)信号通路的调控机制。方法将大鼠随机分为假手术组(Sham组)、模型组(Model组)、低剂量Rem组(Rem-L组)、中剂量Rem组(Rem-M组)、高剂量Rem组(Rem-H组)和高剂量Rem加HMGB1激活剂地塞米松(DEX)组(Rem-H+DEX组),每组15只。除Sham组外,其他各组大鼠均通过升高眼压法构建RIRI模型。采用苏木素-伊红(HE)染色法观察各组大鼠视网膜组织结构变化;采用TUNEL法检测视网膜组织细胞凋亡情况;采用酶联免疫吸附试验(ELISA)法检测各组大鼠血清白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)表达水平;使用试剂盒检测氧化应激指标[超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)]水平;采用蛋白质印迹法(Western blot)检测视网膜组织中缺氧相关因子[缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)]及HMGB1/RAGE/NF-κB信号通路相关蛋白表达水平。结果相较于Sham组,Model组大鼠视网膜高度水肿,神经节细胞数量显著减少,细胞呈现空泡样变化且排列紊乱,细胞间隙增宽;随着Rem注射剂量的增加,RIRI大鼠视网膜水肿程度逐渐减轻,神经节细胞数量增多,排列更加有序。相较于Sham组,Model组大鼠视网膜细胞凋亡率和血清IL-1β、IL-6、TNF-α水平及视网膜组织中MDA、HMGB1、RAGE、NF-κB、HIF-1α、VEGF表达水平均升高,而SOD、GSH-PX表达水平降低,差异有统计学意义(P<0.05);相较于Model组,Rem-L组、Rem-M组和Rem-H组大鼠视网膜细胞凋亡率和血清IL-1β、IL-6、TNF-α水平及视网膜组织中MDA、HMGB1、RAGE、NF-κB、HIF-1α、VEGF表达水平呈剂量依赖性降低,而SOD、GSH-PX表达水平呈剂量依赖性升高,差异有统计学意义(P<0.05);相较于Rem-H组,Rem-H+DEX组上述指标变化趋势逆转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-αand increased expression levels of MDA,HMGB1,RAGE,NF-κB,HIF-1αand VEGF in retinal tissue,while the expression levels of SOD and GSH-PX

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 

分 类 号：R774[医药卫生—眼科] R971[医药卫生—临床医学] R319