右美托咪定通过MAPK/STAT3通路对AD大鼠海马神经元凋亡的影响  

Impact of dexmedetomidine on apoptosis of rat hippocampal neurons induced by Aβ1-42 via MAPK/STAT3 pathway

作　　者：张苗 董彦海 崔子慧 ZHANG Miao;DONG Yanhai;CUI Zihui(Department of Anesthesiology,Baoding Second Hospital,Baoding 071000,China)

机构地区：[1]保定市第二医院麻醉科,河北保定071000

出　　处：《中风与神经疾病杂志》2023年第2期113-117,共5页Journal of Apoplexy and Nervous Diseases

基　　金：保定市科技计划项目(2141ZF012)。

摘　　要：目的探索右美托咪定(Dex)通过丝裂原活化蛋白激酶(MAPK)/信号转导和转录激活子3(STAT3)通路对β-淀粉样蛋白(Aβ)1-42致大鼠海马神经元凋亡的影响。方法随机分为假手术组、Aβ1-42组、Dex低剂量(Dex-L)组、Dex高剂量(Dex-H)组、Dex-H+Anisomycin组、Dex-H+colivelin组,给予不同给药处理后进行实验观察。结果Aβ1-42组大鼠海马组织神经元结构疏松,胞体形态异常,Aβ沉积严重,逃避潜伏期、炎性因子(IL-1β、IL-6、TNF-α)水平、细胞凋亡数目、p-p38 MAPK/p38 MAPK、p-STAT3/STAT3、cleaved caspase-3表达较假手术组均显著增加,穿越原平台次数、Bcl-2表达显著下降(P<0.05);经不同剂量Dex干预后均可逆转上述指标(P<0.05);MAPK通路激活剂及STAT3激活剂可减轻Dex对AD大鼠的保护作用(P<0.05)。结论Dex可以通过减少炎性因子水平以及Aβ沉积,降低细胞损伤和凋亡,保护大鼠海马神经元,可能与抑制MAPK/STAT3通路有关。Objective To explore the impact of dexmedetomidine(Dex)on the apoptosis of rat hippocampal neurons induced byβ-amyloid(Aβ)1-42 via mitogen-activated protein kinase(MAPK)/signal transduction and transcriptional activators 3(STAT3)pathway.Metuods The patients were randomly divided into sham operation group,Aβ1-42、Dex(Dex-L)、Dex(Dex-H)、Dex-H+Anisomycin、Dex-H+colivelin group.The experimental observation was carried out after different treatment of administration.Results In the Aβ1-42 group,the neuronal structure of the hippocampus of rats in the Aβ1-42 group was lost,the cell body morphology was abnormal,and the Aβdeposition was severe,the escape latency,the levels of inflammatory factors(IL-1β,IL-6,TNF-α),the number of apoptotic cells,the expressions of p-p38 MAPK/p38 MAPK,p-STAT3/STAT3,and cleaved caspase-3 were unusually higher than those in the sham operation group,the times of crossing the original platform and the expression of Bcl-2 were unusually lower(P<0.05);the above indicators could be reversed after intervention with different doses of Dex(P<0.05);MAPK pathway activators and STAT3 activators could alleviate the protective effect of Dex on AD rats(P<0.05).Conclusion Dex can reduce the levels of inflammatory factors and Aβdeposition to reduce cell damage and apoptosis,and protect rat hippocampal neurons,which may be related to the inhibition of MAPK/STAT3 pathway.

关 键 词：右美托咪定 MAPK/STAT3通路 AΒ1-42 海马神经元 

分 类 号：R749.1[医药卫生—神经病学与精神病学]