Page 13 - 南京医科大学学报自然科学版

第41卷第8期 南京医科大学学报（自然科学版）
2021年8月 Journal of Nanjing Medical University（Natural Sciences） ·1115 ·

·基础医学·

CAMK4⁃EGR3 信号轴对先天性甲状腺功能减退症大鼠海马神

经元树突的影响

唐青英，赵 捷，李海英，申飞飞，吴尤佳 *
南通大学附属医院儿内科，江苏 南通 226001

［摘 要］ 目的：探讨先天性甲状腺功能减退症（congenital hypothyroidism，CH）大鼠海马中Ca /钙调蛋白依赖性蛋白激酶Ⅳ
2+
（Ca /calmodulin⁃dependent protein kinase Ⅳ，CAMK4）及早期生长反应蛋白3（early growth response protein 3，EGR3）信号轴对神
2+
经元树突发育的影响。方法：1日龄、7日龄及21日龄SD 大鼠制备CH 模型，分为CH 组与对照组。采用转录组测序、q⁃PCR、
Western blot 分别检测 CAMK4 与 EGR3 的表达情况，细胞免疫荧光观察神经元树突生长情况。结果：①对照组海马组织
CAMK4及EGR3的蛋白表达呈时间依赖性上升，CH组的表达则显著低于对照组（P < 0.05）；②原代海马神经元中敲降CAMK4
后，EGR3的表达相应降低，同时海马神经元树突平均长度较对照组减小；③CH原代海马神经元给予三碘甲腺原氨酸（3，5，3′⁃
triiodothyronine，T3）刺激后，CAMK4 的蛋白表达水平呈时间依赖性上升。结论：甲状腺激素缺乏会导致大鼠海马 CAMK4 及
EGR3表达降低，从而抑制神经元树突的发育，表明CAMK4⁃EGR3信号轴可能在CH大鼠海马神经发育异常中发挥重要作用。
［关键词］ 先天性甲状腺功能减退症；海马；树突；CAMK4；EGR3
［中图分类号］ Q451 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）08⁃1115⁃06
doi：10.7655/NYDXBNS20210802

Effects of CAMK4⁃EGR3 signaling axis on hippocampal neuronal dendrites in congenital
hypothyroidism rats

TANG Qingying，ZHAO Jie，LI Haiying，SHEN Feifei，WU Youjia *
Department of Pediatrics，Affiliated Hospital of Nantong University，Nantong 226001，China

［Abstract］ Objective：This stndy aims to investigate the effect of CAMK4⁃EGR3 signaling axis on neuronal dendritic development
in the hippocampus of congenital hypothyroidism（CH）rats. Methods：The CH models were established in 1⁃day⁃old，7⁃day⁃old and 21⁃
day⁃old SD rats，and were divided into CH group and control group. Transcriptome sequencing，q⁃PCR and Western blot were used to
detect the expression of CAMK4 and EGR3，and immunofluorescence was used to observe the growth of neuronal dendrites. Results：①
The protein expressions of CAMK4 and EGR3 in the hippocampus of the control group increased in a time dependent manner，and the
expression of CH group was significantly lower than that of the control group（P < 0.05）；②After CAMK4 was knocked down in the
primary hippocampal neurons，the expression of Egr3 was decreased correspondently，and the mean length of dendrites of hippocampal
neurons was decreased compared with the control group；③ After T3 stimulation on CH primary hippocampal neurons，the protein
expression level of CAMK4 increased in a time dependent manner. Conclusion：Thyroid hormone deficiency can decrease the
expression of CAMK4 and EGR3 in the hippocampus of rats，and inhibit the development of neuronal dendrites，suggesting that the
CAMK4⁃EGR3 signaling axis plays an important role in the neurodevelopmental abnormalities in the hippocampus of CH rats.
［Key words］ congenital hypothyroidism；hippocampus；dendrites；CAMK4；EGR3
［J Nanjing Med Univ，2021，41（08）：1115⁃1120］

［基金项目］ 国家自然青年科学基金（81700696）；江苏省十三五“科教强卫工程”青年医学重点人才（QNRC2016684）；江苏省
333工程科研项目资助计划（BRA2020396）；南通市科技局社会民生科技重点项目（MS22019002，MS22020002）
∗
通信作者（Corresponding author），E⁃mail：francis_nt@163.com