通过抑制糖皮质激素受体缓解应激后抑郁样行为的研究
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1.徐州医科大学法医学教研室;2.徐州医科大学基础医学院法医学教研室

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江苏省重点实验室开放课题;徐州市科技计划


Mifepristone relieving stress induced depressive-like beha-veior through inhibits glucocorticoid receptors
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    摘要:

    目的:为深入研究抑郁症的发病机制,本文探讨了米非司酮(Mifepristone;RU486)与中缝背核区域内糖皮质激素(Glucocorticoid ; GC)受体在调控抑郁样行为症状中的作用,为抑郁症的治疗提供新的治疗靶点。 方法:将8周龄健康雄性C57BL/6J小鼠32只分为对照组(n=8)、模型组(n=8)、RU486组(n=8)和溶媒组(n=8)。首先采用单一刺激禁锢法建立应激小鼠模型,采用高架十字迷宫实验和悬尾实验检测小鼠行为学改变,然后选取中缝背核脑组织制备冰冻切片,采用免疫荧光染色等方法检测小胶质细胞和糖皮质激素受体的激活情况。结果:(1)高架十字迷宫实验结果表明,与对照组相比,模型组小鼠处于闭臂的时间要明显增多,差异具有统计学意义(P<0.05)。悬尾实验结果表明:与对照组相比,模型组小鼠静止时间明显增加,差异具有统计学意义(P<0.01)。(2)免疫荧光染色结果显示应激后小鼠中缝背核区域内GC受体数量增加(P<0.01)同时应激后中缝背核区域内小胶质细胞数量上升(P<0.01),且激活增多(P<0.01)。(3)腹腔注射RU486后,可见中缝背核区域内GC受体数量减少(P<0.01),小胶质细胞数量无明显改变(P>0.05),激活降低(P<0.01),抑郁样行为学表现减轻。结论:RU486通过调解中缝背核区域内小胶质细胞激活,缓解抑郁样行为,为治疗抑郁症提供了新的治疗靶点和治疗药物。

    Abstract:

    To investigate the neural circuit of depressive symptoms derived from glucocorticoid (GC) receptor in dorsal raphe nucleus. Methods: Firstly,build the mice stress model was established, and the experiment has been divided into four groups: control group , Stresssd group, Mifepristone-treated group and Vehicle group, then injected GC receptor antagonists to test the change of inflammatory cytokines which associated with depression. The single-stimulate method was used to form the stress-state and the Behavioral test methods were used to assess the anxiety levels. Immunofluorescence was utilized to detect the GC receptors, microglial activation. Results: (1) Compared with the control group, the immunofluorescence result showed that the number of GC receptors in dorsal raphe nucleus has been increased after stress stimulate. (2) After intraperitoneal injected the GC receptor antagonists (Mifepristone; RU486) , the amount of GC receptors , activated microglial cells had all been decreased in the dorsal raphe nucleus of the mice, and the depression-like behaviors were also attenuated. CONCLUSION: The above results indicated that the Mifepristone in the regulation of microglial cell activation in dorsal raphe nucleus and eventually reduce depression-like behavior.

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  • 收稿日期:2023-03-10
  • 最后修改日期:2023-05-07
  • 录用日期:2023-08-09
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