EGCG对孤独症小鼠小脑浦肯野细胞及行为学的影响

doi:10.6040/j.issn.1671-7554.0.2025.0514

摘要/Abstract

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。

关键词: 表没食子儿茶素没食子酸酯, 孤独症谱系障碍, 小脑, 浦肯野细胞, 行为学

Abstract: 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.

Key words: Epigallocatechin-3-gallate, Autism spectrum disorder, Cerebellum, Purkinje cell, Behavioral

中图分类号:

R749

杨贺旻,孙茂林,刘适,殷玥,张娜,张明龙. EGCG对孤独症小鼠小脑浦肯野细胞及行为学的影响[J]. 山东大学学报 (医学版), 2026, 64(1): 43-56.

YANG Hemin, SUN Maolin, LIU Shi, YIN Yue, ZHANG Na, ZHANG Minglong. Effects of EGCG on cerebellar Purkinje cells and behavioral phenotypes in a mouse model of autism spectrum disorder[J]. Journal of Shandong University (Health Sciences), 2026, 64(1): 43-56.

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