瑞马唑仑对术后认知功能障碍小鼠的神经保护作用

Neuroprotective effect of remimazolam on mice with postoperative cognitive dysfunction

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摘要目的探讨瑞马唑仑对术后认知功能障碍(POCD)小鼠的神经保护作用。方法雄性C57/BL6小鼠30只随机分为三组,每组10只。A组术前腹腔注射瑞马唑仑10mg/kg和生理盐水0.1mL/10g, B组术前仅腹腔注射生理盐水0.1mL/10g,两组行异氟烷麻醉下胫骨骨折内固定术建立POCD小鼠模型;C组仅腹腔注射生理盐水0.1mL/10g作为空白对照。采用旷场实验、Y迷宫实验和Morris水迷宫实验分别评估三组小鼠自发运动能力、认知功能及空间学习能力。应用HE染色和尼式染色观察三组小鼠海马组织中神经元损伤及其形态结构,实时定量PCR检测三组小鼠海马组织中炎症因子IL-6、IL-1β及TNF-α mRNA表达。结果三组小鼠自发运动能力相仿(P>0.05)。与C组比较,A组和B组小鼠交替次数和进臂次数减少,自发交替率降低,潜伏期缩短,平台象限访问时间延长,平台进入次数增加,海马组织中损伤神经元百分比升高而阳性神经元百分比降低,海马组织中IL-1β、IL-6及TNF-α mRNA表达升高(P<0.05或P<0.01)。A组上述指标均优于B组(P<0.01)。结论瑞马唑仑通过抑制神经炎症,从而对POCD小鼠发挥神经保护作用。 Objective To explore the neuroprotective effect of remimazolam on the mice with postoperative cognitive dysfunction(POCD).Methods Thirty male C57/BL6 mice were randomly divided into three groups with 10 mice each.Remimazolam 10 mg/kg and normal saline 0.1 mL/10 g were intraperitoneally injected before the operation in group A,while only normal saline 0.1 mL/10 g was intraperitoneally injected before the operation in group B.Both groups underwent internal fixation of tibial fractures to establish POCD mice model.Only normal saline 0.1 mL/10 g was intraperitoneally injected in group C as the blank control.The open field test,Y-maze test and Morris water maze test were performed to evaluate the spontaneous motor ability,cognitive function and spatial learning ability of the mice,respectively.HE staining and Niss staining were performed to observe the neuronal injury and its morphological structure in hippocampal tissues,as well as real time quantitative PCR was performed to detect mRNA expressions of the inflammatory factors of IL-6,IL-1βand TNF-αin the hippocampal tissues of the mice in three groups.Results The spontaneous motor abilities of mice in three groups were similar(P>0.05).Compared with group C,the number of alternation and arm entry times were decreased,the spontaneous alternation rate was decreased,latency was shortened,access time to the platform quadrant was prolonged,the number of platform entry times was increased,the percentage of injured neurons was increased,while the percentage of positive neurons was decreased in the hippocampal tissues,and mRNA expressions of IL-6,IL-1βand TNF-αwere increased in group A and group B(P<0.05 or P<0.01).The above indicators in group A were all better than those in group B(P<0.01).Conclusion Remimazolam has neuroprotective effects on POCD mice by inhibiting neuroinflammation.

作者秦芳芳陈筱诗蒋琦胡鹏超罗辉宇 QIN Fangfang;CHEN Xiaoshi;JIANG Qi;HU Pengchao;LUO Huiyu(Department of Anesthesiology,Xiangyang No.1 People's Hospital,Jinzhou Medical University Union Training Base,Xiangyang 441000,CHINA)

机构地区锦州医科大学湖北医药学院附属襄阳市第一人民医院研究生联合培养基地麻醉科湖北医药学院附属襄阳市第一人民医院麻醉科

出处《江苏医药》 2025年第7期656-659,664,F0002,F0003,共7页 Jiangsu Medical Journal

基金湖北省自然科学基金创新新发展联合基金项目(2024AFD059)。

关键词瑞马唑仑术后认知功能障碍小鼠 Remimazolam Postoperative cognitive dysfunction Mouse

分类号 R614 [医药卫生—麻醉学]

作者简介通信作者:罗辉宇,E-mail:603983267@qq.com。