地塞米松致子代大鼠海马轴突发育损伤  

Dexamethasone-induced Hippocampal Axon Developmental Damage in Offspring Rats

作　　者：谢露露 姚宝珍[1] XIE Lulu;YAO Baozhen(Department of Pediatrics,Renmin Hospital of Wuhan University,Wuhan 430000,China)

机构地区：[1]武汉大学人民医院儿科,武汉430000

出　　处：《生物技术进展》2022年第3期467-472,共6页Current Biotechnology

基　　金：武汉大学医学腾飞计划(TFLC2018001)。

摘　　要：为了探讨地塞米松对子代大鼠海马轴突的影响,建立了孕期地塞米松暴露(prenatal dexamethasone exposure,PDE)模型。Wistar大鼠于孕中晚期皮下注射地塞米松(0.2 mg·kg^(-1)·d^(-1)),部分子代于孕20天(GD20)、出生后12周(PW12)处死取海马样本,检测海马糖皮质激素受体(glucocorticoid receptor,GR)活化指标以及轴突损伤指标。PDE子代胎鼠海马GR活化,GR、糖皮质激素调节激酶1(glucocorticoid-regulated kinase 1,SGK1)和FK506结合蛋白(FK506 binding protein 5,FKBP5)表达显著增加。轴突损伤指标包括生长相关蛋白43(growth associated protein-43,GAP43)、信号素3A(semaphorin 3A,SEMA3A)和集聚蛋白(agrin)表达明显升高。而PDE成年子代大鼠海马GR无明显活化,轴突损伤指标GAP43、SEMA3A和AGRIN表达明显升高。研究结果证实PDE通过活化胎海马GR引起轴突发育损伤,且轴突损伤可延续至出生后。In order to explore the effect of dexamethasone on the hippocampal axons of offspring rats,a prenatal dexamethasone exposure(PDE)model was established.Wistar rats were subcutaneously injected with dexamethasone(0.2 mg·kg^(-1)·d^(-1))in the second and third trimesters,some offspring were sacrificed during the gestational days of 20(GD20)and at postnatal week of 12(PW12),and the hippocampal glucocorticoid receptors(GR)activation index and axon damage index were detected.GR was ac⁃tivated in the hippocampus of PDE offspring,and the expressions of GR,glucocorticoid-regulated kinase 1(SGK1)and FK506 binding protein 5(FKBP5)were significantly increased.Axon damage indicators including growth-associated protein-43(GAP43),semaphorin 3A(SEMA3A)and agrin expression were significantly increased.However,the hippocampal GR of PDE adult offspring rats was not significantly activated,and the expressions of axonal injury indicators GAP43,SEMA3A and AGRIN were significantly increased.The results comfirmed that PDE induces axonal developmental damage by activating fetal hippocam⁃pal GR,and axonal damage can persist after birth.

关 键 词：糖皮质激素受体 海马 轴突损伤 神经疾病 

分 类 号：R742.8[医药卫生—神经病学与精神病学]