艾片联合橄榄苦苷通过TLR4/MyD88/NF-κB信号通路对脑缺血-再灌注损伤大鼠的脑保护机制研究  

Study on the Protective Mechanism of Aipian Combined with Oleuropein on Cerebral Ischemia-reperfusion Injury in Rats Through TLR4/MyD88/NF-κB Signaling Pathway

作　　者：董建将 孟楠 刘佳奇 常乐 DONG Jianjiang;MENG Nan;LIU Jiaqi;CHANG Le(Basic Medical College,Mudanjiang Medical University,Mudanjiang 157011,Heilongjiang,China;College of Phar-macy,Mudanjiang Medical University,Mudanjiang 157011,Heilongjiang,China)

机构地区：[1]牡丹江医科大学基础医学院,黑龙江牡丹江157011 [2]牡丹江医科大学药学院,黑龙江牡丹江157011

出　　处：《系统医学》2025年第1期41-44,49,共5页Systems Medicine

基　　金：牡丹江市科技局应用技术研究与开发计划项目(HT2022JG124);2023年度黑龙江省省属高等学校基本科研业务费项目(2023-KYYWF-0944)。

摘　　要：目的探讨艾片联合橄榄苦苷(oleuropein,OLE)通过TLR4/MyD88/NF-κB信号通路对脑缺血-再灌注损伤(cerebral ischemia reperfusion injury,CIRI)大鼠的脑保护机制。方法选取牡丹江医科大学医药研究中心购买的50只SD大鼠作为研究对象,随机分成假手术组、模型组、艾片组、OLE组、艾片+OLE组,每组10只,采用颈总动脉夹闭法制备CIRI大鼠模型。缺血1 h后再灌注24 h。采用伊文思蓝染色法检测大鼠血脑屏障通透性,酶标仪比色法检测大鼠脑组织总谷胱甘肽(total glutathione,T-GSH)、丙二醛(malondialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)水平;酶联免疫吸附测定法检测大鼠血清中肿瘤坏死因子α(tu⁃mor necrosis factor-α,TNF-α)、白介素1β(interleukin 1β,IL-1β)的含量;实时荧光定量聚合酶链反应检测闭锁小带蛋白1(zonula occludens-1,ZO-1)、紧密连接咬合蛋白(Occludin)、Toll样受体4(toll-like receptors 4,TLR4)、髓样分化因子88(myeloid differentiation factor88,MyD88)和核因子κB(nuclear factorκB,NF-κB)mRNA表达水平。结果艾片组、OLE组、艾片+OLE组伊文思蓝、MDA、TNF-α、IL-1β的含量低于模型组,TLR4、MyD88、NF-κB的mRNA表达水平低于模型组,ZO-1和Occludin的mRNA表达水平、T-GSH和SOD的含量高于模型组,差异有统计学意义(P均<0.05)。结论艾片联合OLE可以减轻CIRI大鼠脑损伤,其作用机制可能与改善血脑屏障通透性和氧化应激损伤,抑制TLR4/MyD88/NF-κB信号通路有关。Objective To investigate the protective mechanism of Aipian combined with oleuropein(OLE)on cerebral ischemia-reperfusion injury(CIRI)in rats through TLR4/MyD88/NF-κB signaling pathway.Methods Fifty SD rats purchased from the Medical Research Center of Mudanjiang Medical University were randomly divided into sham op⁃eration group,model group,Aipian group,OLE group and Aipian+OLE group,with ten rats in each group.The CIRI rat model was prepared by common carotid artery occlusion.Ischemia for 1 h and reperfusion for 24 h.Total glutathi⁃one (T-GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by Evans blue staining and colorimetric assay in rat brain tissue. The levels of tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were measured by enzyme-linked immunosorbent assay in rat serum. Real-time fluorescence quantitative polymerase chain reaction was used to detect the levels of zonula occludens-1 (ZO-1), Occludin, toll-like receptors 4 (TLR4), myeloid differentiation factor88 (MyD88), and the level of interleukin 1β (IL-1β), and nuclear factor κB (NF-κB) mRNA ex⁃ pression levels. Results The levels of Evans Blue, MDA, TNF-α and IL-1β in Aipian group, OLE group, and Aipian + OLE group were lower than those in the model group;the mRNA expression levels of TLR4, MyD88 and NF-κB mRNA were lower than those in the sham operation group, and the mRNA expression levels of ZO-1 and Occludin, and the contents of T-GSH and SOD were higher than those of the model group, and the differences were statistically significant (all P<0.05). Conclusion Aipian combined with OLE can reduce brain injury in CIRI rats, and its mecha⁃ nism may be related to improving blood-brain barrier permeability and oxidative stress injury, and inhibiting TLR4/ MyD88/NF-κB signaling pathway.

关 键 词：艾片 橄榄苦苷 脑缺血-再灌注损伤 氧化损伤 炎症 

分 类 号：R4[医药卫生—临床医学]