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

发布时间：2018-11-15 07:24

【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 1receptor,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(P0.05)、和糖水偏好率均显著下降(P0.05),在穿格次数、站立次数、修饰次数均少于对照组(P0.05);而治疗组与对照组以上实验结果无统计学差异(P0.05)。束缚应激组血浆CRH浓度较对照组升高(P0.05),但治疗组血浆CRH浓度较对照组无统计学差异(P0.05)。束缚应激组下丘脑BDNF、GAP-43表达较对照组与治疗组增多(P0.05)。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 study the effects of restraint stress on the expression of brain-derived neurotrophic factor (brain derived neurotrophic factor,BDNF) and growth-associated protein (growth associated protein 43) in rat hypothalamus. The role of BDNF and GAP-43 in the development of depression-like symptoms induced by chronic stress and the therapeutic effect of CP-154526 were analyzed. Methods Thirty male SD rats were randomly divided into three groups: restraint stress group, CP-154526 treatment group and control group. The depression model was established in the restraint stress group by 3 hours per day for 21 days, and the adrenocorticotropic hormone releasing hormone 1 receptor (corticotrophin-releasing hormone type 1 receptor) was used to establish the depression model. CRH1R) CP-154526 treatment group has been treated with CP-154526 since the experiment, and the control group has been injected with DMSO., the solvent of CP-154526. The changes of behavior and the expression of BDNF,GAP-43 protein in hypothalamus of model rats were detected by enzyme linked immunosorbent assay (Elisa) and plasma corticotropin releasing hormone (corticotropin releasing hormonecorti,CRH) concentration; Western blot. Results compared with the control group and the treatment group, the growth of body mass in the restraint stress group decreased (P0.05), and the preference rate of sugar water decreased significantly (P0.05), and the number of piercing, standing and modification in the control group was lower than that in the control group (P0.05). But the treatment group and the control group above experiment result has no statistical difference (P0.05). The plasma CRH concentration in the restraint stress group was higher than that in the control group (P0.05), but the plasma CRH concentration in the treatment group was not significantly different from that in the control group (P0.05). The expression of BDNF,GAP-43 in hypothalamus in restraint stress group was higher than that in control group and treatment group (P0.05). Conclusion chronic restraint stress can increase the expression of BDNF,GAP-43 protein in hypothalamus and induce plasticity of hypothalamus. CP-154526 can reverse the expression of BDNF and GAP-43 protein in hypothalamus and ameliorate depressive symptoms.
【作者单位】：第三军医大学大坪医院野战外科研究所老年科;第三军医大学大坪医院野战外科研究所神经外科;
【基金】：重庆市自然科学基金(cstc2013jj B10002)~~
【分类号】：R965

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