灯盏花素通过抑制TLR4/NF-κB通路减轻后循环缺血性眩晕大鼠脑组织损伤  

Breviscapine alleviates brain tissue damage in rats with posterior circulation ischemic vertigo by inhibiting TLR4/NF-κB pathway

作　　者：刘巧丽[1] 刘晓豆 耿永芝 李勇[1] LIU Qiaoli;LIU Xiaodou;GENG Yongzhi;Li Yong(Chengde Central Hospital,Chengde 067000,Hebei,China)

机构地区：[1]承德市中心医院,河北承德067000

出　　处：《西部医学》2023年第10期1452-1458,共7页Medical Journal of West China

基　　金：河北省医学科学研究课题(20201282)。

摘　　要：目的探讨灯盏花素(Bre)对后循环缺血性眩晕(PCIV)大鼠脑组织损伤的影响及其机制。方法将80只Wistar大鼠随机分为假手术(Sham)组、模型(PCIV)组、Bre组(2 mg/kg)、TAK242[Toll样受体4(TLR4)抑制剂]组(3 mg/kg)和Bre+TAK242组(2 mg/kg+3 mg/kg),每组16只。采用结扎右侧颈总动脉和右侧锁骨下动脉的方法复制PCIV大鼠模型,各组分别1次/d腹腔注射(ip)给药治疗7 d。测定逃避电刺激潜伏期、前庭神经核血流量和血液流变学指标,通过HE染色和TUNEL染色观察海马神经元病理改变和神经元凋亡,比色法检测海马组织乳酸(Lac)、乳酸脱氢酶(LDH)和炎症因子(IL-1β、TNF-α、IFN-γ)含量,Western blot法检测TLR4、核因子κB p65(NF-κB p65)、磷酸化NF-κB p65(p-NF-κB p65)、IκBα、p-IκBα蛋白表达。结果与PCIV组相比,Bre组和TAK242组逃避电刺激潜伏期缩短、前庭神经核血流量升高(P<0.05);全血(低切、中切、高切)黏度、血浆黏度、红细胞压积(HCT)、红细胞聚集指数(EAI)、血沉(ESR)降低且红细胞变形指数(EDI)升高(均P<0.05);海马神经元数量减少、排列疏松紊乱、胞核固缩偏移深染、边界不清等病理改变明显改善,神经元凋亡数量明显减少(均P<0.05);海马组织Lac、LDH、IL-1β、TNF-α、IFN-γ含量降低,TLR4表达量及NF-κB p65、IκBα磷酸化率(p-NF-κB p65/NF-κB p65、p-IκBα/IκBα)降低(均P<0.05)。Bre+TAK242组对上述指标的作用明显优于Bre组和TAK242组(P<0.05)。结论Bre可减轻PCIV大鼠眩晕症状,改善前庭神经核血流量,减轻脑组织损伤,作用机制可能与抑制TLR4/NF-κB信号通路介导炎症反应有关。Objective To investigate the effect and mechanism of Breviscapine(Bre)on posterior circulation ischemic vertigo(PCIV).Methods 80 Wistar rats were randomly divided into sham group,model group,Bre group(2 mg/kg),TAK242[toll-like receptor 4(TLR4)inhibitor]group(3 mg/kg)and Bre+TAK242 group(2 mg/kg+3 mg/kg),n=16.The PCIV rat models were established by ligating the right common carotid artery and right subclavian artery,and the drugs were given by intraperitoneal injection(ip)once a day for 7 days.The latency to escape from electrical stimulation,blood flow of vestibular nerve nucleus and hemorheological indexes were measured;the pathological changes and apoptosis of hippocampal neurons were observed by HE staining and TUNEL staining;the content of lactate(Lac),lactate dehydrogenation(LDH)and inflammatory factors(IL-1β,TNF-α,IFN-γ)in hippocampus were detected by colorimetry;the protein expression of TLR4,nuclear factorκB p65(NF-κB p65),phosphorylated NF-κB p65(p-NF-κB p65),IκBα,p-IκBαwere detected by Western blot.Results Compared with the PCIV group,the escape latency in Bre group and TAK242 group were shortened and the vestibular nucleus blood flow were increased(P<0.05);the whole blood viscosity(low shear,medium shear,high shear),plasma viscosity,hematocrit(HCT),erythrocyte aggregation index(EAI),erythrocyte sedimentation rate(ESR)were decreased and the erythrocyte deformability index(EDI)was increased(P<0.05);the pathological changes of hippocampal neurons such as the numbers decreased,the arrangement was loose and disordered,the pyknotic pyknosis was shifted and hyperchromatic,the boundary was unclear and other pathological changes were significantly improved;the number of apoptotic hippocampal neurons were significantly decreased;the content of Lac,LDH,IL-1β,TNF-α,IFN-γin hippocampus were decreased,the expression of TLR4 and the phosphorylation ratio of NF-κB p65,IκBα(p-NF-κB p65/NF-κB p65,p-IκBα/IκBα)were decreased(P<0.05).The effect of Bre+TAK242 on the detection indexes above were signif

关 键 词：灯盏花素 缺血性眩晕 前庭神经核血流量 血液流变学 TLR4/NF-κB通路 炎症反应 

分 类 号：R285.5[医药卫生—中药学]