早期多感觉刺激对缺氧缺血性脑损伤新生大鼠海马p-ERK/p-CREB/BDNF/TrkB信号通路的影响  

Effects of early multisensory stimulation on the p-ERK/p-CREB/BDNF/TrkB signaling pathway in the hippocampus of neonatal rats with hypoxic-ischemic brain damage

作　　者：蒋心如 凌晨 祁芳[1] 曾学究 佘艳 唐暹 易细芹 艾坤[1] JIANG Xinru;LING Chen;QI Fang;ZENG Xuejiu;SHE Yan;TANG Xian;YI Xiqin;AI Kun(School of Acupuncture-moxibustion,Tuina and Rehabilitation,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;The First People's Hospital of Chenzhou City,Chenzhou,Hunan 423000,China)

机构地区：[1]湖南中医药大学针灸推拿与康复学院,湖南长沙410208 [2]郴州市第一人民医院,湖南郴州423000

出　　处：《湖南中医药大学学报》2024年第11期1999-2006,共8页Journal of Hunan University of Chinese Medicine

基　　金：湖南省残疾人康复科研项目(2019XK017);湖南中医药大学医学技术一流学科开放基金项目(2018YXJS05)。

摘　　要：目的观察早期多感觉刺激对缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)新生大鼠海马区磷酸化的细胞外信号调节激酶(phosphorylated extracellular signal-regulated kinase,p-ERK)/磷酸化的环磷腺苷效应元件结合蛋白(phosphorylated cAMP-response element binding protein,p-CREB)/脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)/酪氨酸激酶受体B(tyrosinekinase receptor B,TrkB)信号途径及其介导的突触重塑的影响。方法将48只7日龄健康新生大鼠以随机数字表法分为假手术组、模型组、早期多感觉刺激组,每组16只。模型组和早期多感觉刺激组大鼠制备HIBD模型,假手术组仅暴露颈总动脉。早期多感觉刺激组自造模24 h开始施以持续28 d的早期多感觉刺激干预,余组不进行处理。采用水迷宫实验检测各组大鼠空间学习和记忆能力;透射电镜观察海马突触亚微结构变化;免疫组织化学法检测大鼠海马BDNF、TrkB表达水平;Western blot检测各组大鼠海马中p-ERK、p-CREB、BDNF、TrkB、突触蛋白1(Synapsin1,Syn1)的蛋白表达水平。结果与假手术组比较,模型组新生大鼠训练第3、4、5天逃避潜伏时间显著延长(P<0.01),训练第6天穿越平台次数显著减少(P<0.01);海马突触亚微结构模糊不清,突触密度降低,突触小泡减少;海马p-ERK、p-CREB、BDNF、TrkB、Syn1蛋白表达水平显著下调(P<0.01)。与模型组比较,早期多感觉刺激组新生大鼠训练第4、5天逃避潜伏时间显著缩短(P<0.01),训练第6天穿越平台次数增多(P<0.05);海马突触密度增加,突触连接增多,突触前膨大可见清亮圆形的突触小泡;海马p-ERK、p-CREB、BDNF、TrkB、Syn1蛋白表达水平显著上调(P<0.01)。结论早期多感觉刺激可有效促进新生缺氧缺血性脑损伤大鼠认知功能,促进缺血侧海马突触重塑,其作用机制可能与激活p-ERK/p-CREB/BDNF/TrkB信号通路有关。Objective To observe the effects of early multisensory stimulation on the signaling pathway of phosphorylated extracellular signal-regulated kinase(p-ERK)/phosphorylated cAMP-response element binding protein(p-CREB)/brain-derived neur-otrophic factor(BDNF)/tyrosine kinase receptor B(TrkB)and its mediated synaptic remodeling in the hippocampus of neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods Forty-eight healthy seven-day-old neonatal rats were randomized into sham-operated group,model group,and early multisensory stimulation group,with 16 rats in each group.A HIBD model was establ-ished in the model and early multisensory stimulation groups.The sham-operated group only had the common carotid arteries exposed without further intervention.The early multisensory stimulation group received continuous early multisensory stimulation interventions for 28 days starting 24 h post-modeling,while the other groups did not receive any treatment.Morris water maze test was performed to assess the spatial learning and memory ability of rats;transmission electron microscopy was utilized to observe changes in hippocampal synaptic ultrastructure;immunohistochemistry was used to measure the expression levels of BDNF and TrkB in the hippocampus;Western blot was employed to analyze the protein expression levels of p-ERK,p-CREB,BDNF,TrkB,and Syn1 in the hippocampus.Results Compared with the sham-operated group,the model group showed significantly prolonged escape latencies on training days 3,4,and 5(P<0.01)and a significantly reduced number of platform crossings on training day 6(P<0.01);the hippocampal synaptic ultrastructure was blurred,with decreases in synaptic density and synaptic vesicles;the protein expression levels of p-ERK,p-CREB,BDNF,TrkB,and Syn1 in the hippocampus were significantly downregulated(P<0.01).Compared with the model group,the early multisensory stimulation group exhibited shorter escape latencies on training days 4 and 5(P<0.01)and an increased number of platform crossings on training day 6(P<0.

关 键 词：新生缺氧缺血性脑损伤 早期多感觉刺激 突触重塑 磷酸化的细胞外信号调节激酶 磷酸化的环磷腺苷效应元件结合蛋白 脑源性神经营养因子 

分 类 号：R285.5[医药卫生—中药学]