miR-125a-5p通过靶向STAT3减轻戊四唑诱导的癫痫大鼠神经功能障碍和炎症反应  

miR-125a-5p attenuates neurological dysfunction and inflammatory responses in pentylenetetrazole-induced epileptic rats by targeting STAT3

作　　者：单萍[1] 张继龙[1] SHAN Ping;ZHANG Jilong(Wuhan First Hospital,Wuhan 430022,China)

机构地区：[1]武汉市第一医院,武汉430022

出　　处：《中国免疫学杂志》2024年第7期1373-1380,共8页Chinese Journal of Immunology

基　　金：国家自然科学基金(81703870)。

摘　　要：目的:探讨miR-125a-5p通过靶向信号转导与转录激活因子3(STAT3)对戊四唑(PTZ)诱导的癫痫大鼠神经功能障碍和炎症反应的影响。方法:采用PTZ点燃法建立大鼠癫痫模型,并将其随机分为6组:Con组、PTZ组、PTZ+agomir NC组、PTZ+miR-125a-5p agomir组、PTZ+miR-125a-5p agomir+pcDNA组和PTZ+miR-125a-5p agomir+pc-STAT3组,评价miR-125a-5p对大鼠癫痫持续时间、潜伏期、惊厥次数和严重程度的影响。qRT-PCR检测miR-125a-5p和STAT3 mRNA表达;改良神经系统严重程度评分(mNSS)、开场实验和Rotarod测试评价癫痫大鼠的神经功能;Morris水迷宫实验评价癫痫大鼠的认知功能;免疫染色观察海马CA1和CA3区域神经元凋亡;ELISA检测海马组织炎症因子(TNF-α、IL-6、IL-1β和IL-18)水平;Western blot检测海马组织中STAT3蛋白表达;双荧光素酶实验验证miR-125a-5p和STAT3的关系。结果:在PTZ诱导的癫痫大鼠中,miR-125a-5p表达上调,STAT3表达下调,且miR-125a-5p靶向抑制STAT3表达。与PTZ组相比,PTZ+miR-125a-5p agomir组癫痫大鼠的潜伏期缩短,癫痫评分降低,癫痫发作时间和次数减少,mNSS降低,掉落潜伏期及外围区域的移动距离、开放区域的总距离延长,逃避潜伏期显著降低,穿越平台次数及停留在目标象限的时间和游泳距离均增加,海马组织TNF-α、IL-6、IL-1β、IL-18表达降低,CA3和CA1区的NenN+细胞增多(P<0.05);STAT3过表达可逆转miR-125a-5p agomir对癫痫大鼠神经功能障碍及炎症反应的缓解作用(P<0.05)。结论:miR-125a-5p通过靶向下调STAT3,减轻PTZ诱导的癫痫大鼠神经功能障碍和炎症反应。Objective:To investigate the impacts of miR-125a-5p on neurological dysfunction and inflammatory response in pentylenetetrazole(PTZ)-induced epileptic rats by targeting signal transducer and activator of transcription 3(STAT3).Methods:Rats epilepsy models were established by PTZ ignition method and randomly grouped into six groups:Con group,PTZ group,PTZ+agomir NC group,PTZ+miR-125a-5p agomir group,PTZ+miR-125a-5p agomir+pcDNA group and PTZ+miR-125a-5p agomir+pc-STAT3 group.Impacts of miR-125a-5p on epilepsy duration,latency,number and severity of seizures in rats were evaluated.qRTPCR was applied to detect miR-125a-5p and STAT3 mRNA expressions;Modified Nervous System Severity Score(mNSS),open field test and Rotarod test were applied to evaluate neurological function in epileptic rats;Morris water maze test was applied to evaluate cognitive function of epileptic rats;immunostaining was applied to observe neuronal apoptosis in hippocampal CA1 and CA3 regions;ELISA was applied to detect levels of inflammatory factors(TNF-α,IL-6,IL-1βand IL-18)in hippocampus;Western blot was applied to detect STAT3 protein expression in hippocampus;dual-luciferase assay was applied to verify the relationship between miR-125a-5p and STAT3.Results:In PTZ-induced epilepsy rats,expression of miR-125a-5p was up-regulated,while expression of STAT3 was down-regulated,and miR-125a-5p was targeted and inhibited expression of STAT3.Compared with PTZ group,PTZ+miR-125a-5p agomir group had shorter latency,lower epilepsy score,fewer seizure duration and times,lower mNSS,increased fall latency and movement distance in peripheral areas and total open area,greatly decreased escape latency,increased number of platform crossings and time spent in the target quadrant and swimming distance,reduced expressions of TNF-α,IL-6,IL-1β,IL-18 in hippocampus,and increased NenN+cells in CA3 and CA1 regions(P<0.05);overexpression of STAT3 could reverse the alleviating effects of miR-125a-5p agomir on neurological dysfunction and inflammatory response in epil

关 键 词：miR-125a-5p 信号转导与转录激活因子3 戊四唑 癫痫 神经功能障碍 炎症 

分 类 号：R742.1[医药卫生—神经病学与精神病学]