瑞马唑仑减轻七氟烷诱导的老年大鼠认知障碍的机制研究  

The mechanism of remimazolam in attenuating sevoflurane-induced cognitive impairment in aged rats

作　　者：宋盼盼 于丽丽[1] SONG Panpan;YU Lili(Department of Anesthesiology,Cangzhou Central Hospital,Cangzhou 061000,Hebei Province,China)

机构地区：[1]沧州市中心医院麻醉科,河北沧州061000

出　　处：《世界临床药物》2025年第1期29-37,共9页World Clinical Drug

基　　金：2022年度河北省医学科学研究课题(20220339)。

摘　　要：目的探讨瑞马唑仑调节Toll样受体(toll-like receptor,TLR)4/髓样分化因子(myeloid differentiation factor,MyD)88/核转录因子-κB(nuclear factor,NF)-κB通路对七氟烷诱导的大鼠认知功能障碍的影响。方法72只雄性SD大鼠分为A~F组,每组12只。A组(50%空气和氧气混合物,2 L/min),其他组在A组+2%七氟烷构建老年术后认知功能障碍大鼠模型。建模成功后,C~E组分别(1.5 mg/kg、3 mg/kg以及6 mg/kg瑞马唑仑+腹腔注射等量生理盐水);F组(6 mg/kg瑞马唑仑+腹腔注射75μg RS09);A、B组大鼠尾静脉和腹腔均注射等量的生理盐水。观察大鼠逃避潜伏期、穿越平台数及海马组织病理;免疫荧光染色检测离子化钙结合适配分子(ionized calcium-binding adapter molecule,IBA)-1表达;酶联免疫吸附试验检测海马组织中神经元特异性烯醇化酶(neuron-specific enolase,NSE)、白介素(interleukin,IL)-6、中枢神经特异蛋白S-100β、肿瘤坏死因子(tumor necrosis factor,TNF)-α水平;原位末端转移酶标记法检测神经元凋亡;免疫印记法检测TLR4、MyD88、裂解的天冬氨酸特异性半胱氨酸蛋白酶(Cleaved Caspase)-3、p-NF-κB p65蛋白。结果与B组相比,C~E组大鼠神经元排列紊乱及细胞形态变化有所改善,逃避潜伏期缩短,穿越平台数增加,NSE、S-100β、IL-6、TNF-α水平、IBA-1阳性细胞数、神经元凋亡率及TLR4、MyD88、Cleaved Caspase-3、p-NF-κB p65蛋白降低(P<0.05)。结论瑞马唑仑可能通过抑制TLR4/MyD88/NF-κB通路改善七氟烷诱导的老年大鼠认知功能障碍。Objective To investigate the effect of remimazolam on cognitive dysfunction induced by sevoflurane in rats by regulating Toll-like receptor(TLR)4/myeloid differentiation factor(MyD)88/nuclear transcription factor(NF)-κB pathway.Methods A total of 72 male SD rats were divided into A to F groups,12 rats in each group.A group(50%air and oxygen mixture,2 L/min)and other groups were treated with A group+2%sevoflurane to construct aged postoperative cognitive dysfunction rat model.After successful modeling,C groups to E were given(1.5 mg/kg,3 mg/kg and 6 mg/kg remimazolam+intraperitoneal injection of the same amount of 0.9%sodium chloride injection),respectively,F group was given(6 mg/kg remimazolam+intraperitoneal injection of 75μg RS09).The rats in A group and B group were injected with the same amount of 0.9%sodium chloride injection in the tail vein and abdominal cavity.The escape latency,the number of crossing platforms and the histopathology of hippocampus were observed.The expression of ionized calcium-binding adapter molecule(IBA)-1 was detected by immunofluorescence staining.Enzyme-linked immunosorbent assay was used to detect the levels of neuron-specific enolase(NSE),interleukin(IL)-6,central nervous system specific protein S-100β,and tumor necrosis factor(TNF)-αin hippocampus.Terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to detect neuronal apoptosis.TLR4,MyD88,Cleaved caspase-3 and p-NF-κB p65 proteins were detected by immunoblotting.Results Compared with B group,the disordered arrangement of neurons and cell morphological changes of rats in C~E group were improved,the escape latency was shortened,and the number of crossing platforms was increased.Levels of NSE,S-100β,IL-6,TNF-α,the number of IBA-1 positive cells,neuronal apoptosis rate,and the proteins levels of TLR4,MyD88,Cleaved Caspase-3,and p-NF-κB p65 were significantly decreased(P<0.05).Conclusion Remimazolam may improve sevoflurane-induced cognitive dysfunction in aged rats by inhibiting the T

关 键 词：瑞马唑仑 Toll样受体4/髓样分化因子88/核转录因子-κB通路 术后认知功能障碍 神经炎症 凋亡 

分 类 号：R-33[医药卫生]