ICG-001对大鼠孤独症样行为及海马树突棘形态发育的影响  

Effects of ICG-001 on autistic behaviors and the development of hippocampal dendritic spine morphology in rats

作　　者：王潇娜 梅道启 罗淑颖 高超[3] 张耀东 Wang Xiaona;Mei Daoqi;Luo Shuying;Gao Chao;Zhang Yaodong(Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Henan Key Laboratory of Children′s Genetics and Metabolic Diseases,Henan Children′s Neurodevelopment Engineering Research Center,Zhengzhou 450053,China)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院郑州儿童医院,河南省儿童遗传代谢性疾病重点实验室,河南省儿童神经发育工程研究中心,郑州450053 [2]郑州大学附属儿童医院神经内科,郑州450018 [3]郑州大学附属儿童医院康复科,郑州450053

出　　处：《中华实用儿科临床杂志》2023年第2期140-145,共6页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(81901387);河南省科技攻关计划项目(212102310034);河南省医学科技攻关计划联合共建项目(LHGJ20210632);河南省儿童神经发育工程研究中心开放课题(SG202202)。

摘　　要：目的探讨ICG-001对大鼠孤独症样行为及海马锥体神经元树突棘形态发育的影响。方法健康雌性Wistar大鼠自然受孕,出生子代大鼠依据随机数字表法分为4组:生理盐水对照组、ICG-001对照组、丙戊酸钠(VPA)组和ICG-001处理组。每组12只。运用三箱社交、埋珠、旷场和高架十字迷宫实验检测大鼠社交、重复刻板和焦虑样行为。应用免疫荧光检测大鼠海马CA1区神经特异核蛋白(NeuN)阳性神经元数目。高尔基染色法观察大鼠海马锥体神经元树突棘密度和形态改变。Western blot检测大鼠海马磷酸化LIM激酶1(LIMK1)、肌动蛋白结合蛋白(Cofilin)、纤维状肌动蛋白(F-actin)和脑发育调节蛋白A(Drebrin A)蛋白表达。采用单因素方差分析统计学差异,以Tukey法进行组间比较。结果1.三箱社交行为实验:生理盐水对照组、ICG-001对照组、VPA组和ICG-001处理组与新奇大鼠接触时间分别为(219.42±5.38)s、(218.67±10.12)s、(126.58±5.02)s、(218.58±6.63)s,偏好指数分别为0.43±0.05、0.43±0.04、0.22±0.01、0.42±0.04;与VPA组相比,ICG-001处理组接触时间及偏好指数均显著增加(均P<0.05)。2.埋珠实验:4组大鼠埋珠数量分别为(9.13±0.52)个、(9.08±0.64)个、(15.13±0.82)个、(9.42±0.86)个;与VPA组相比,ICG-001处理组埋珠数量显著减少(P<0.05)。3.旷场实验:4组大鼠的中央区域停留时间分别为(82.33±1.83)s、(81.32±4.19)s、(45.51±3.02)s、(81.44±3.19)s;与VPA组相比,ICG-001处理组中央区域停留时间明显增加(P<0.05)。4.高架十字迷宫实验:4组大鼠在开臂停留时间分别为(107.75±7.23)s、(106.08±7.50)s、(63.42±1.91)s、(106.67±7.07)s;与VPA组相比,ICG-001处理组在开臂停留时间显著增加(P<0.05)。5.免疫荧光实验:4组大鼠海马CA1区NeuN阳性神经元数量分别为(41.83±1.17)×10^(4)/μm^(2)、(41.00±0.77)×10^(4)/μm^(2)、(27.17±0.95)×10^(4)/μm^(2)、(40.00±0.90)×10^(4)/μm^(2);与VPA组相比,ICG-001处理组NObjective To explore the effects of the compound ICG-001 on autism-like behaviors and the morphological development of dendritic spines in hippocampal pyramidal neurons of rats.Methods Healthy Wistar rats were mated.The offspring were divided into the saline-treated group,ICG-001 control group,Sodium valproate(VPA)group and ICG-001 treatment group by using the random number table method.Each group had 12 rats.Social interaction,repetitive,compulsive and anxiety-like behaviors in rodents were assessed by three-chambered social approach,marble burying,open-field and elevated plus maze tests.The number of neuronal nuclei(NeuN)-positive neurons in the hippocampal CA1 region was calculated by the immunofluorescence method.Golgi staining was carried out to detect the density and morphological changes of dendritic spines in hippocampal pyramidal neurons of rats.The expression of phosphorylated LIM kinase 1(LIMK1),phosphorylated actin binding protein(Cofilin),fibros actin(F-actin)and developmentally-regulated brain protein A(Drebrin A)was examined by Western blot.The univariate analysis was made to examine whether the difference was statistically significant,and the data between groups were compared by the Tukey method.Results(1)In the three-chambered social approach test,the rats in the saline-treated group,ICG-001 control group,VPA group and ICG-001 treatment group spent(219.42±5.38)s,(218.67±10.12)s,(126.58±5.02)s,and(218.58±6.63)s in the chamber,respectively.The corresponding preference score of the said 4 groups were 0.43±0.05,0.43±0.04,0.22±0.01 and 0.42±0.04,respectively.Compared with the VPA group,the ICG-001 treatment group spent longer time in the chamber and had a higher preference score(all P<0.05).(2)In the marble burying experiment,the number of marbles buried in said 4 groups were 9.13±0.52,9.08±0.64,15.13±0.82 and 9.42±0.86,respectively.ICG-001-treated rats buried markedly less marbles than VPA-exposed rats(P<0.05).(3)In the open-field test,the rats in the said 4 groups spent(82.33±1.83)s,(81

关 键 词：孤独症 ICG-001 树突棘 LIM激酶1/肌动蛋白解聚因子通路 脑发育调节蛋白A 

分 类 号：R749.94[医药卫生—神经病学与精神病学]