基于CREB/BDNF信号通路探讨NA-1对新生大鼠缺氧缺血性脑损伤的保护作用  

Protective Effect of NA-1 on Hypoxic-ischemic Brain Damage in Neonatal Rats Based on CREB/BDNF Signaling Pathway

作　　者：夏莉[1] 阴怀清[1] 阴崇娟[1] 白丹 师睿[1] XIA Li;YIN Huaiqing;YIN Chongjuan;BAI Dan;SHI Rui(First Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi,China)

机构地区：[1]山西医科大学第一医院,太原030001

出　　处：《中西医结合心脑血管病杂志》2025年第2期223-227,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：山西省卫生健康委科研计划项目(No.2022027)。

摘　　要：目的:探讨突触后密度蛋白-95(PSD-95)抑制剂(NA-1)对新生大鼠缺氧缺血性脑损伤(HIBD)海马区环磷酸腺苷反应元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)信号通路的影响。方法:将7 d龄新生SD大鼠随机分为正常对照组、HIBD组、NA-1组(腹腔注射10μg/g NA-1溶液)和NA-1+CREB抑制剂H89组(腹腔注射10μg/g NA-1溶液+2μg/L H89溶液),每组15只。采用Rice法制备HIBD模型,评估大鼠神经行为变化;2,3,5-三苯基氯化四氮唑(TTC)染色和尼氏染色观察大鼠脑组织病理变化;蛋白免疫印迹法(Western Blot)检测大鼠海马区PSD-95和CREB/BDNF信号通路表达情况。结果:与正常对照组比较,HIBD组大鼠趋地反射和悬崖逃避反射时间延长,前肢握力时间缩短,脑梗死体积、海马区PSD-95蛋白表达增加,尼氏阳性细胞数、磷酸化CREB(p-CREB)/CREB、BDNF蛋白表达减少(P<0.05);与HIBD组比较,NA-1组趋地反射和悬崖逃避反射时间缩短,前肢握力时间延长,脑梗死体积、海马区PSD-95蛋白表达减少,尼氏阳性细胞数、p-CREB/CREB、BDNF蛋白表达增加(P<0.05);添加H89可部分逆转NA-1的作用。结论:NA-1可改善新生大鼠HIBD后的神经行为,减少脑梗死体积和神经元凋亡,可能与激活CREB/BDNF信号通路有关。Objective:To investigate the effect of postsynaptic densitin-95(PSD-95)inhibitor(NA-1)on cyclic adenosine phosphate response element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in hippocampus of neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods:Neonatal SD rats of 7 d-old were randomly divided into normal control group,HIBD group,NA-1 group(intraperitoneally injected with 10μg/g NA-1 solution)and NA-1+CREB inhibitor H89 group(intraperitoneally injected with 10μg/g NA-1 solution+2μg/L H89 solution),with 15 rats in each group.HIBD model was established by Rice method to evaluate the neurobehavioral changes of rats.The 2,3,5-triphenyltetrazolium chloride(TTC)staining and Nissl staining were used to observe the pathological changes of rat brain.The expression of PSD-95 and CREB/BDNF signaling pathway in the hippocampus of rats was detected by Western Blot.Results:Compared with the normal control group,the time of ground reflex and cliff escape reflex in the HIBD group was prolonged,the time of forelimb grip strength was shortened,the volume of cerebral infarction and the expression of PSD-95 protein in hippocampus increased,and the number of Nissl positive cells,phosphorylated CREB(p-CREB)/CREB and BDNF protein decreased(P<0.05).Compared with the HIBD group,the time of ground reflex and cliff escape reflex in the NA-1 group was shortened,the time of forelimb grip strength was prolonged,the volume of cerebral infarction and the expression of PSD-95 protein in hippocampus decreased,and the number of Nissl positive cells,p-CREB/CREB and BDNF protein were increased(P<0.05),while adding H89 partially reversed the effect of NA-1.Conclusion:NA-1 could improve the neurobehavior of neonatal rats after HIBD,reduce the volume of cerebral infarction and neuronal apoptosis,which might be related to the activation of CREB/BDNF signaling pathway.

关 键 词：新生儿缺氧缺血性脑损伤 突触后密度-95抑制剂 环磷酸腺苷反应元件结合蛋白/脑源性神经营养因子信号通路 神经元损伤 大鼠 实验研究 

分 类 号：R722.1[医药卫生—儿科]