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糖皮质激素受体功能对注意缺陷多动障碍模型鼠行为的影响
卢洪珠, 章飞霞, 洪晓文, 王闽莹, 黄靓, 郑杰, 陈燕惠
中国当代儿科杂志 ›› 2018, Vol. 20 ›› Issue (10) : 848-853.
PDF(1028 KB)
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糖皮质激素受体功能对注意缺陷多动障碍模型鼠行为的影响
Effect of glucocorticoid receptor function on the behavior of rats with attention deficit hyperactivity disorder
目的 通过比较自发性高血压大鼠（SHR）与Wistar Kyoto（WKY）大鼠及Sprague-Dawley（SD）大鼠行为学方面的差异，探讨注意缺陷多动障碍（ADHD）亚型理想的动物模型及糖皮质激素受体（GR）功能对ADHD大鼠的影响。方法 将生后21 d的24只SHR雄性大鼠随机分为GR激动剂组、GR抑制剂组和SHR组（n=8）；另以生后21 d的WKY雄性大鼠、SD雄性大鼠各8只分别作为WKY组和SD组。GR激动剂组予以地塞米松（DEX）腹腔注射（每日0.5 mg/kg）；GR抑制剂组予以米非司酮（RU486）腹腔注射（每日54 mg/kg）；SHR组、WKY组和SD组则均予以生理盐水腹腔注射（每日0.5 mL/kg），连续用药14 d。根据开场实验和Lat迷宫评估各组大鼠自发活动程度和非选择性注意水平。结果 开场实验结果显示：药物干预前，SHR穿越格子数、直立次数较WKY大鼠及SD大鼠明显增多（P < 0.05）；WKY大鼠穿越格子数显著多于SD大鼠（P < 0.05），但理毛次数SD大鼠显著多于WKY大鼠（P < 0.05）。药物干预后，GR激动剂组穿越格子数和理毛次数较SHR组明显减少（P < 0.05）。Lat迷宫结果显示：药物干预前，SHR穿越角落数和直立次数较WKY大鼠及SD大鼠明显增多（P < 0.05）；WKY大鼠较SD大鼠直立次数和斜搭次数明显增多（P < 0.05）。药物干预后，GR激动剂组穿越角落数和直立次数较SHR组均显著减少（P < 0.05）；GR抑制剂组直立次数较SHR组增加（P < 0.05）；与SD组比较，WKY组大鼠直立次数及斜搭次数增多（P < 0.05）。结论 SHR是ADHD混合型亚型的理想动物模型，WKY大鼠能否作为ADHD注意力缺陷型亚型的动物模型仍有待于进一步研究；GR激动剂可有效改善SHR自发活动行为和非选择性注意水平。
Objective To investigate the ideal animal models for attention deficit hyperactivity disorder (ADHD) subtypes and the effect of glucocorticoid receptor (GR) function on the behavior of ADHD rats by comparing behavioral differences between spontaneously hypertensive rats (SHRs), Wistar Kyoto (WKY) rats, and Sprague-Dawley (SD) rats. Methods A total of 24 male SHRs aged 21 days were randomly divided into GR agonist group, GR inhibitor group, and SHR group, with 8 rats in each group. Eight male WKY rats and 8 male SD rats, also aged 21 days, were enrolled as WKY group and SD group respectively. The GR agonist group was treated with intraperitoneal injection of dexamethasone (0.5 mg/kg daily); the GR inhibitor group was treated with intraperitoneal injection of mifepristone (RU486)(54 mg/kg daily); the SHR, WKY, and SD groups were treated with intraperitoneal injection of normal saline (0.5 mL/kg daily). The course of treatment was 14 days for all groups. The open field test and Lat maze test were used to evaluate spontaneous activity and non-selective attention. Results The open field test showed that before drug intervention the SHR group had significantly higher numbers of line crossings and rearings than the WKY and SD groups (P < 0.05); the WKY group had a significantly higher number of line crossings than the SD group (P < 0.05); the SD group had a significantly higher number of groomings than the WKY group (P < 0.05). After drug intervention, the GR agonist group had significantly lower numbers of line crossings and groomings than the SHR group (P < 0.05). The Lat maze test indicated that before drug intervention the SHR group had significantly higher numbers of corner crossings and rearings than the WKY and SD groups (P < 0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P < 0.05). After drug intervention, the GR agonist group had significantly lower numbers of corner crossings and rearings than the SHR group (P < 0.05); the GR inhibitor group had a significantly higher number of rearings than the SHR group (P < 0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P < 0.05). Conclusions SHR is an ideal animal model for mixed subtype ADHD, and further studies are needed to determine whether WKY rats can be used as an animal model for attention-deficit subtype ADHD. GR agonist can effectively improve spontaneous activity and non-selective attention in SHRs.
Attention deficit hyperactivity disorder / Glucocorticoid receptor / Rats
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国家自然科学基金（81371262）。
