摘要
目的探究腹腔注射表没食子儿茶素没食子酸酯(epigallocatechin-3-gallate,EGCG)对丙戊酸钠(valproic acid,VPA)诱导孤独症子代小鼠小脑浦肯野细胞形态和孤独症样行为的影响。方法构建VPA小鼠模型,腹腔注射EGCG,通过HE染色,免疫荧光实验观察EGCG对VPA诱导的孤独症谱系障碍(autism spectrum disorder,ASD)小鼠小脑浦肯野细胞病理学的影响。通过行为学方法(三箱社交实验、旷场实验、高架十字迷宫实验、新物体识别实验、Morris水迷宫实验)观察正常组小鼠、VPA组小鼠和VPA+EGCG组小鼠、社交水平、自发活动、焦虑以及学习记忆的差异。结果HE染色和免疫荧光实验表明,腹腔注射EGCG可逆转VPA诱导子代ASD小鼠小脑浦肯野细胞数量减少和病理学改变;三箱社交实验中,腹腔注射EGCG可改善VPA诱导子代ASD小鼠的社交倾向性障碍和新奇社交偏好;旷场实验和高架十字迷宫实验中,EGCG可减轻VPA诱导子代ASD小鼠在新异环境中的自发活动和焦虑状态;新物体识别实验中,EGCG能改善VPA诱导子代ASD小鼠对新物体识别和记忆能力缺陷;Morris水迷宫实验中,EGCG可缓解VPA诱导子代ASD小鼠对空间学习记忆功能障碍。结论EGCG减轻VPA诱导子代ASD小鼠小脑浦肯野细胞数量和病理学改变,改善ASD小鼠孤独症样行为障碍。
Objective To explore the effects of intraperitoneal epigallocatechin-3-gallate(EGCG)on cerebellar Purkinje cell morphology and autism-like behaviors in valproic acid-induced autistic offspring mice.Methods A valproic acid(VPA)-induced mouse model of autism spectrum disorder(ASD)was established.Following intraperitoneal injection of epigallocatechin-3-gallate(EGCG),hematoxylin and eosin(H&E)staining and immunofluorescence were performed to evaluate the effects of EGCG on VPA-induced pathological changes in cerebellar Purkinje cells.Behavioral tests including the three-chamber social interaction test,open field test,elevated plus maze test,novel object recognition test,and Morris water maze test were performed to assess differences in social behavior,spontaneous locomotor activity,anxiety-like behaviors,and learning/memory performance among control mice,VPA-exposed mice,and VPA+EGCG-treated mice.Results H&E staining and immunofluorescence analyses revealed that intraperitoneal administration of EGCG reversed VPA-induced reductions in cerebellar Purkinje cell density and ameliorated pathological alterations in offspring ASD model mice.In the three-chamber social test,EGCG administration improved social preference deficits and restored novelty-induced social interaction in VPA-exposed mice.Behavioral assessments further demonstrated that EGCG significantly reduced hyperactivity in novel environments(open field test)and alleviated anxiety-like behaviors(elevated plus maze test)in VPA-induced offspring.Additionally,EGCG enhanced novel object recognition memory in the novel object recognition test and mitigated spatial learning and memory impairments in the Morris water maze.Conclusion EGCG treatment ameliorates the VPA-induced reduction in the number of cerebellar Purkinje cells and the associated pathological changes in the cerebellum of offspring autistic mice,resulting in an improvement in ASD-like behavioral abnormalities.
作者
杨贺旻
孙茂林
刘适
殷玥
张娜
张明龙
YANG Hemin;SUN Maolin;LIU Shi;YIN Yue;ZHANG Na;ZHANG Minglong(Central Laboratory,The Third Affiliate Hospital of Qiqihar Medical University,Qiqihar 161006,Heilongjiang,China;Office of the President,The Third Affiliate Hospital of Qiqihar Medical University,Qiqihar 161006,Heilongjiang,China;Scientific Research Department,The Third Affiliate Hospital of Qiqihar Medical University,Qiqihar 161006,Heilongjiang,China;Department of Radiation Oncology,The Third Affiliate Hospital of Qiqihar Medical University,Qiqihar 161006,Heilongjiang,China;Department of Genetics,Qiqihar Medical University,Qiqihar 161006,Heilongjiang,China)
出处
《山东大学学报(医学版)》
2026年第1期43-56,共14页
Journal of Shandong University(Health Sciences)
基金
黑龙江省省属高等学校基本科研业务费科研项目(2022-KYYWF-0795)
黑龙江省省属本科高校“优秀青年教师基础研究支持计划”项目(YQJH2024279)
齐齐哈尔医学院科学院(博士专项)项目(QMSI2024B-04)
齐齐哈尔医学院重点培育项目(2025-ZDPY-005)。
