基础医学与临床 ›› 2018, Vol. 38 ›› Issue (9): 1231-1238.

• 研究论文 • 上一篇    下一篇

下丘脑-垂体-肾上腺轴紊乱对焦虑性抑郁模型大鼠海马结构的影响

凌佳1,吴梦瑶1,杨琴2,赵洪庆1,杜青1,韩远山1,王宇红1   

  1. 1. 湖南中医药大学
    2. 湖南中医药大学第一附属医院
  • 收稿日期:2017-06-28 修回日期:2017-11-09 出版日期:2018-09-05 发布日期:2018-09-10
  • 通讯作者: 王宇红 E-mail:wyh107@126.com
  • 基金资助:
    基于Glu-mGluR2.3介导的海马NVU联动损伤研究糖尿病并发抑郁症发病机制及中药干预;基于SGK1研究抑郁症海马隔颞轴神经元再生障碍及中药干预;焦虑抑郁共病动物模型及其多层次评价体系建立与中药干预

Effect of hypothalamus pituitary adrenal axis disorder on hippocampal formation in rats with anxious depression

  • Received:2017-06-28 Revised:2017-11-09 Online:2018-09-05 Published:2018-09-10

摘要: 目的 研究HPA轴紊乱对焦虑性抑郁模型大鼠海马结构的影响,探讨焦虑性抑郁的潜在发病机制。 方法 将大鼠随机分为空白组、溶媒组、焦虑组、抑郁组和焦虑性抑郁组,每组12只。采用慢性束缚应激联合皮质酮注射方法建立焦虑性抑郁大鼠模型,连续21 d;造模后采用高架十字迷宫(EPM)、旷场实验(OFT)、强迫游泳实验(FST)评价大鼠焦虑和抑郁样行为,HE染色检测大鼠HPA轴各组织及海马病理变化,ELISA法检测大鼠血浆中促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量,Western blot检测大鼠海马糖皮质激素受体(GR)蛋白表达。 结果 焦虑性抑郁组大鼠进入开臂的时间、次数及自主活动次数均与焦虑组相当,不动时间显著增加,与对照组及抑郁组比较有显著差异(P<0.01或P<0.05);HPA轴各组织均出现不同程度损伤,海马神经元肿胀,呈空泡状;同时,血浆中CRH、ACTH和CORT含量显著增加(P<0.01或P<0.05),海马GR表达显著下降。 结论 焦虑性抑郁模型组大鼠具有显著的焦虑及抑郁样行为,其发病机制可能与机体HPA轴紊乱及其引发的脑内海马损伤密切相关。

关键词: 焦虑性抑郁, 焦虑性抑郁模型, HPA轴紊乱, 病理变化, 糖皮质激素受体

Abstract: Objective To study the effect of HPA axis disorder on the hippocampal formation in rats with anxious depression and to explore its potential pathogenesis. Methods Rats were randomly divided into control group, vehicle group, anxiety group, depression group and anxious depression group, 12 rats in each group. Anxious depression rats were intervened by chronic restraint stress combined with corticosterone injection for continuous 21 d. Then, elevated plus maze (EPM), open field test (OFT), forced swimming test (FST) were used to evaluate the anxious and depression like behavior in rats, HE staining to check pathological changes of the HPA axis tissue and hippocampus. The plasma levels of CRH, ACTH and CORT of rats were detected by ELISA, and the expression of GR in hippocampus was detected by Western blot. Results Compared with control group and depression group, there were significant differences (P<0.01 or P<0.05) in OE% and OT% at EPM and independent activity frequency during OFT, which was similar to anxious depression group. Compared with control group and anxious group, the immobility time in FST was increased significantly (P<0.01). HE staining showed that all tissues of HPA axis were damaged in different degrees, and the hippocampal neurons were swollen and vacuolated. Conclusions Ansious depression rats had significant anxious and depressive behaviors, which pathogenesis may be closely related to the HPA axis disorder and hippocampus region damage.

Key words: anxious depression, anxious depression model, HPA axis disorder, pathological change, glucocorticoid receptor