摘要
目的分析瑞马唑仑对脓毒症神经损伤保护作用及机制分析。方法研究样本选取27只成年雄性大鼠,随机分为对照组、模型组及研究组,对照组进行假手术,模型组建立脓毒症神经损伤模型,研究组在其基础上给予瑞马唑仑腹腔注射。观察各组大鼠水迷宫实验结果并检测各组大鼠脑病理学变化、神经元凋亡率、IL-6、IL-10、TNF-α水平及CHOP、TATF4、XBP1 mRNA和IκBα、IKK、NF-κB蛋白相对表达。结果术前各组水迷宫实验结果差异无统计学意义(P>0.05),术后各组逃避潜伏期、平台穿越次数比较差异有统计学意义(P<0.05),对照组逃避潜伏期低于模型组及研究组,平台穿越次数高于模型组及研究组;研究组逃避潜伏期低于模型组,平台穿越次数高于模型组(P<0.05);苏木精-伊红染色结果显示,对照组脑组织无明显病理变化,模型组病理变化严重;研究组较模型组病理变化改善;各组神经元凋亡率比较差异有统计学意义(P<0.05),对照组低于模型组及研究组;研究组低于模型组(P<0.05);各组IL-6、IL-10、TNF-α水平比较差异有统计学意义(P<0.05),对照组IL-6、IL-10、TNF-α水平低于模型组及研究组;研究组IL-6、IL-10、TNF-α水平低于模型组(P<0.05);各组CHOP、TATF4、XBP1 mRNA比较差异有统计学意义(P<0.05),对照组CHOP、TATF4、XBP1 mRNA低于模型组及研究组;研究组CHOP、TATF4、XBP1 mRNA低于模型组(P<0.05);对照组IκBα、IKK、NF-κB蛋白相对表达量显著低于模型组及研究组,研究组IκBα、IKK、NF-κB蛋白相对表达量显著低于模型组(P<0.05)。结论瑞马唑仑可通过抑制脓毒症大鼠内质网应激、神经炎症及神经细胞凋亡实现神经保护作用,减少脓毒症大鼠神经损伤,其作用机制可能与IKK/NF-κB信号通路有关。
Objective To analyze the protective effect of remazolam on nerve injury in sepsis and its mecha⁃nism.Methods 27 adult male rats were randomly divided into control group,model group and study group.Sham operation was performed in the control group,sepsis nerve injury model was established in the model group,and the study group was given intraperitoneal injection of remazolam.The results of water maze experiment were observed and brain pathological changes,neuronal apoptosis rate,levels of IL⁃6,IL⁃10,TNF⁃α,mRNA of CHOP,TATF4,XBP1 and protein of IκBα,IKK,NF⁃κB were detected.Results There was no statistically significant difference in the results of water maze experiment among all groups before surgery(P>0.05),but there were statistically signifi⁃cant differences in escape latency and number of platform crossing among all groups after surgery(P<0.05).The es⁃cape latency of control group was lower than that of model group and research group,and the number of platform crossing was higher than that of model group and research group.The escape latency of study group was lower than that of model group,and the number of platform crossing was higher than that of model group(P<0.05).HE stain⁃ing showed that the brain tissue of the control group had no obvious pathological changes,while the pathological changes of the model group were serious.The pathological changes of the study group were improved compared with the model group.The neuronal apoptosis rate was significantly different among all groups(P<0.05),and the control group was lower than the model group and the research group.The study group was lower than the model group(P<0.05).The levels of IL⁃6,IL⁃10 and TNF⁃αwere significantly different among all groups(P<0.05).The levels of IL⁃6,IL⁃10 and TNF⁃αin control group were lower than those in model group and research group.The levels of IL⁃6,IL⁃10 and TNF⁃αin study group were lower than those in model group(P<0.05).The mRNA levels of CHOP,TATF4 and XBP1 were significantly different among all groups(P<0.05).The mRNA levels of CHOP,TATF4 and XBP1 in control group were lower than those in model group and research group.CHOP,TATF4 and XBP1 mRNA in study group were lower than those in model group(P<0.05).The relative expression of IκBα,IKK,NF⁃κB pro⁃tein in all groups had statistical significance(P<0.05),and the relative expression of IκBα,IKK,NF⁃κB protein in control group was significantly lower than that in model group and research group.The relative expressions of IκBα,IKK and NF⁃κB proteins in the study group were significantly lower than those in the model group(P<0.05).Conclusion Remazolam can achieve neuroprotective effect by inhibiting endoplasmic reticulum stress,neuroinflam⁃mation and nerve cell apoptosis in sepsis rats,and reduce nerve injury in sepsis rats.The mechanism may be related to IKK/NF⁃κB signaling pathway.
作者
李帆
乔辉
LI Fan;QIAO Hui(Department of Anesthesiology,Beijing Shijitan Hospital Affiliated to Capital Medical University,Beijing 100038)
出处
《解剖学研究》
CAS
2024年第3期221-227,共7页
Anatomy Research
基金
北京市附属医院科研培育计划项目(PX2023028)。
作者简介
通讯作者:乔辉,E⁃mail:254317714@qq.com。
