米非司酮通过抑制糖皮质激素受体缓解应激后抑郁样行为的研究  

Mifepristone relieving stress induced depressive-like behaveior through inhibiting glucocorticoid receptors

作　　者：韩雨清 牛海晨 李海英 周阳 包海军 HAN Yuqing;NIU Haicheng;LI Haiying;ZHOU Yang;BAO Haijun(Department of Forensic,the First Clinical Medicine College,Xuzhou Medical University,Xuzhou 221004,China;Department of Genetics,Public Experimental Research Center,Xuzhou Medical University,Xuzhou 221004,China;Department of Pathology,Basic Medicine College,Xuzhou Medical University,Xuzhou 221004,China)

机构地区：[1]徐州医科大学第一临床医学院法医学教研室,江苏徐州221004 [2]徐州医科大学生命科学院遗传学教研室,江苏徐州221004 [3]徐州医科大学基础医学院病理学教研室,江苏徐州221004

出　　处：《南京医科大学学报（自然科学版）》2023年第8期1102-1107,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省重点实验室开放课题(JBSL1703);徐州市科技计划(KC20120)。

摘　　要：目的:探讨米非司酮(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)、溶媒组(n=8)和RU486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,采用免疫荧光染色法检测小胶质细胞和GC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占比明显增多,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<0.05)。②免疫荧光染色结果显示,应激后小鼠中缝背核区域内GC受体荧光占比增加(P<0.05),同时应激后中缝背核区域内小胶质细胞荧光占比上升(P<0.05),且激活荧光占比增多(P<0.05)。③腹腔注射RU486后,可见中缝背核区域内GC受体荧光占比减少(P<0.05),小胶质细胞荧光占比无明显改变(P>0.05)、激活荧光占比降低(P<0.05),抑郁样行为学表现减轻。结论:RU486通过激活中缝背核区域内小胶质细胞,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。Objective:To investigate the neural circuit of depressive symptoms derived from glucocorticoid(GC)receptor in dorsal raphe nucleus.Methods:Firstly,a stress mouse model was established using a single stimulus coufinement method,and the mice were divided into four groups:control group,stresssd group,mifepristone-treated group and vehicle group,then the mice were injected with GC receptor antagonists to test behavioral changes by tail suspension test and elevated plus maze test.Immunofluorescence was utilized to detect the activation of GC receptors and microgial.Results:①Compared with the control group,the immunofluorescence result showed that the number of GC receptors in dorsal raphe nucleus was increased after stress stimulate.②After intraperitoneal injection of the GC receptor antagonists(mifepristone,RU486),the amount of GC receptors and the activated microglial cells were decreased in the dorsal raphe nucleus of the mice,and the depression-like behaviors were also attenuated.Conclusion:The above results indicated that mifepristone regulates microglial cell activation in dorsal raphe nucleus to eventually reduce depression-like behavior.

关 键 词：应激状态 米非司酮 糖皮质激素受体 抑郁样行为 

分 类 号：R363[医药卫生—病理学]