右美托咪定对癫痫大鼠海马神经元细胞凋亡与Toll样受体4/核因子κB信号通路的影响  

Effects of dexmedetomidine on apoptosis and TLR-4/NF-κB signaling pathway in hippocampal neurons of epileptic rats

作　　者：雍芳[1] 狄政莉[1] 贾晓涛[1] 刘志勤[1] 顾乃兵[1] 郝敏锋 燕玉娥 YONG Fang;DI Zhengli;JIA Xiaotao;LIU Zhiqin;GU Naibing;HAO Minfeng;YAN Yu’e(Department of Neurology,Xi’an Central Hospital,Xi’an 710004,China)

机构地区：[1]西安市中心医院神经内科,陕西西安710004

出　　处：《陕西医学杂志》2023年第2期132-135,153,共5页Shaanxi Medical Journal

基　　金：陕西省重点研发计划项目(2022SF-418)。

摘　　要：目的:探讨右美托咪定对癫痫大鼠海马神经元细胞凋亡和Toll样受体4(TLR-4)/核因子κB(NF-κB)信号通路的影响。方法:选择45只健康SD大鼠随机分为A组、B组和C组,各15只。适应饲养1周后给予C组大鼠腹腔注射20μg/kg右美托咪定,给予A组和B组大鼠腹腔注射等体积0.9%氯化钠溶液,均连续腹腔注射7 d。随后B组和C组采用氯化锂-匹罗卡品腹腔注射制作大鼠癫痫模型,A组大鼠不做处理。造模成功1周后进行Morris水迷宫测试。处死大鼠取脑组织,采用TUNEL技术检测海马组织神经元凋亡比例,采用酶联免疫吸附法检测海马组织中肿瘤坏死因子α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)水平,采用Western blot技术检测海马组织中NF-κB、磷酸化NF-κB(pNF-κB)、离子钙结合衔接分子1(Iba-1)、TLR-4相对表达水平。结果:C组各时间点逃避潜伏期显著长于A组,但显著短于B组(均P<0.05);C组大鼠平台穿越次数显著少于A组,多于B组(均P<0.05)。B组和C组大鼠海马组织TNF-α、IL-1β和IL-6水平均显著高于A组,C组大鼠各指标显著低于B组(均P<0.05)。C组大鼠海马神经元凋亡比例显著高于A组,但显著低于B组(均P<0.05)。C组大鼠海马组织pNF-κB、Iba-1和TLR-4蛋白相对表达水平显著高于A组,但显著低于B组(均P<0.05)。结论:右美托咪定不仅可以通过激活TLR-4/NF-κB信号通路抑制癫痫大鼠海马神经元的炎性反应,还可以通过激活TLR-4/NF-κB信号通路下调炎症因子进而抑制癫痫大鼠海马神经元细胞的凋亡,从而改善神经功能,发挥神经保护作用。Objective:To investigate the effects of dexmedetomidine on apoptosis and toll-like receptor 4(TLR-4)/nu clear factor-κB(NF-κB)signaling pathway in hippocampal neurons of epileptic rats.Methods:A total of 45 healthy SD rats were randomly divided into group A,group B and group C,with 15 rats in each group.After one week of adaptation to feeding,rats in Group C were given intraperitoneal injection of 20μg/kg dexmedetomidine,rats in group A and group B were intraperitoneally injected with the same volume of 0.9%sodium chloride solution.All rats were injected intraperitoneally for 7 days.Then group B and group C were intraperitoneally injected with lithium pilocarpine to make epilepsy model,while group A was not treated.Morris water maze test was carried out one week after successful modeling.The rats were killed to take brain tissue and detect the percentage of neuronal apoptosis in hippocampus,and the levels of TNF-α,IL-1βand IL-6 in hippocampus were detected by enzyme-linked immunosorbent assay,and the relative expression levels of NF-κB,pNF-κB,Iba-1,TLR-4 were detected by Western blot.Results:The escape latency of group C at each time point was significantly longer than that of group A,but significantly shorter than that of group B(all P<0.05).The number of platform crossing in group C was significantly less than that in group A,but more than that in group B(all P<0.05).The TNF-α,IL-1βand IL-6 levels in hippocampus of rats in group B and C were significantly higher than those in group A,and the above indexes of rats in group C were significantly lower than those in group B(all P<0.05).The percentage of apoptosis of hippocampal neurons in group C was significantly higher than that in group A,but significantly lower than that in group B(all P<0.05).The relative expression levels of pNF-κB,Iba-1 and TLR-4 proteins in hippocampus of rats in group C were significantly higher than those in group A,but significantly lower than those in group B(all P<0.05).Conclusion:Dexmedetomidine can not only inhibit the infl

关 键 词：右美托咪定 海马神经元 癫痫 细胞凋亡 TOLL样受体4 核因子ΚB 

分 类 号：R581[医药卫生—内分泌]