[1]戴若以,顾小红,张云东,等.阻断促肾上腺皮质激素释放激素1受体对慢性束缚应激致大鼠类抑郁症状的改善[J].第三军医大学学报,2015,37(22):2273-2277.
　Dai Ruoyi,Gu Xiaohong,Zhang Yundong,et al.Blocking corticotropin-releasing hormone 1 receptor regulates expression of BDNF and GAP-43 in hypothalamus of depression rats induced by chronic restraint stress[J].J Third Mil Med Univ,2015,37(22):2273-2277.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
37卷
期数:
2015年第22期
页码:
2273-2277
栏目:
论著
出版日期:
2015-11-30

文章信息/Info

Title:
Blocking corticotropin-releasing hormone 1 receptor regulates expression of BDNF and GAP-43 in hypothalamus of depression rats induced by chronic restraint stress
作者:
戴若以; 顾小红; 张云东; 陈卓
第三军医大学大坪医院野战外科研究所：老年科,神经外科
Author(s):
Dai Ruoyi;  Gu Xiaohong;  Zhang Yundong;  Chen Zhuo

Department of Geriatrics， Department of Neurologic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China

关键词:
束缚应激; 抑郁症; 下丘脑; 脑源性神经生长因子; 生长相关蛋白
Keywords:
restraint stress;  depression;  hypothalamus;  brain derived neurotrophic factor;  growth associated protein 43
分类号:
R-332；R363.271；R749.41
文献标志码:
A
摘要:

目的      研究束缚应激对大鼠下丘脑脑源性神经营养因子（brain derived neurotrophic factor，BDNF）和生长相关蛋白（growth associated protein 43，GAP-43）表达的影响，并分析BDNF和GAP-43在慢性应激致类抑郁样症状发生中的作用以及CP-154526的治疗作用。      方法      将30只雄性SD大鼠随机分成3组，即束缚应激组、CP-154526治疗组和对照组。束缚应激组采用每日束缚3 h、连续21 d的方法建立抑郁症模型，促肾上腺皮质激素释放激素1受体 (corticotrophin-releasing hormone type 1 receptor，CRH1R)阻断剂CP-154526治疗组自实验开始用CP-154526对抑郁模型动物予以治疗，对照组注射CP-154526的溶剂DMSO。观测各组大鼠行为学变化；酶联免疫吸附实验检测血浆促肾上腺皮质激素释放激素（corticotropin releasing hormonecorti, CRH）浓度；Western blot检测模型大鼠下丘脑BDNF、GAP-43蛋白表达表达情况。      结果      束缚应激组与对照组和治疗组相比体质量增长下降（P<0.05）、和糖水偏好率均显著下降（P<0.05），在穿格次数、站立次数、修饰次数均少于对照组（P<0.05）；而治疗组与对照组以上实验结果无统计学差异（P>0.05）。束缚应激组血浆CRH浓度较对照组升高（P<0.05），但治疗组血浆CRH浓度较对照组无统计学差异（P>0.05）。束缚应激组下丘脑BDNF、GAP-43表达较对照组与治疗组增多（P<0.05）。      结论      慢性束缚应激可致大鼠下丘脑BDNF、GAP-43蛋白表达上调，导致下丘脑发生可塑性变化，与下丘脑CRH分泌增多以及抑郁症行为的变化相关。CRH1R阻断剂CP-154526可逆转下丘脑BDNF和GAP-43蛋白的表达,改善类抑郁症状。

Abstract:

Objective      To determine the effect of chronic restraint stress on the expression of brain derived neurotrophic factor (BDNF) and growth associated protein 43 (GAP-43) in the hypothalamus of rats, the role of BDNF and GAP-43 in the pathogenesis of depression induced by chronic restraint stress, and the regulation effect of CP-154526 [corticotrophin-releasing hormone type 1 receptor (CRH1R) antagonist].       Methods      A total of 30 male Sprague-Dawley rats were randomly divided into 3 groups: restraint stress group, CP-154526 treatment group and control group. The rats were restrained for 3 h daily over a period of 21 d to construct depression model. The treatment group was injected with CP-154526 from the beginning of the experiment, while the control group was injected with dimethyl sulfoxide (solvent of CP-154526). Then the behaviors of the rats were observed. The level of corticotrophin-releasing hormone (CRH) in the blood serum was detected by enzyme-linked immunosorbent assay(ELISA), and the expression of BDNF and GAP-43 in the hypothalamus was verified by Western blotting.       Results      Compared with the control group and the CP-154526 treatment group, the restraint stress group showed decreased body weight (P<0.05), reduced sucrose preference (P<0.05), and decreased spanning lattice times, standing times and modification times (P<0.05). There was no statistical difference between the CP-154526 treatment group and the control group in the above tests (P>0.05). The restraint stress group showed significant increase in the serum CRH concentration compared with the control group (P<0.05), but there was no significant difference between the CP-154526 treatment group and the control group (P>0.05). Compared with the control group and CP-154526 treatment group, the restraint stress group showed higher expression of BDNF and GAP-43 in the hypothalamus (P<0.05).       Conclusion      Chronic restraint stress can induce up-regulation of BDNF protein and GAP-43 protein in the hypothalamus, and lead to plastic changes in the hypothalamus, which are consistent with the changes of CRH secretion and depression-related behavior. CP-154526 significantly alleviates the symptoms of depression through inhibiting the up-regulation of BDNF protein and GAP-43 protein in the hypothalamus.

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更新日期/Last Update: 2015-11-21