CAJ | 학술논문

目的观察老年大鼠慢性应激后行为学改变、血皮质醇水平及海马内糖皮质激素受体(GR)、盐皮质激素受体(MR)的变化,探讨下丘脑-垂体-肾上腺轴(HPA轴)功能在老年抑郁症发病机制中的作用. 方法老年Wister雄性大鼠随机分为对照组和造模组,经过4周慢性应激后造模成功.常规取血清检测皮质醇含量,免疫组化检测海马GR、MR表达. 结果造模组大鼠从第2周开始摄食减少,体质量降低,清洁活动减少,旷场得分及糖水摄入量均较对照组降低(P＜0.01).造模组大鼠血皮质醇含量较对照组升高(P＜0.01).造模组海马神经元数量较对照组减少,以CA3区最为明显,而DG区无明显改变;海马CA3区GR阳性细胞数减少,MR阳性细胞数未见明显变化.结论慢性应激导致抑郁老年大鼠HPA轴功能紊乱,血皮质醇含量升高,海马神经元受损,海马组织内GR表达量减少.慢性应激导致的HPA轴功能紊乱在抑郁症发病机制中具有重要作用.
목적 관찰노년대서만성응격후행위학개변、혈피질순수평급해마내당피질격소수체(GR)、염피질격소수체(MR)적변화,탐토하구뇌-수체-신상선축(HPA축)공능재노년억욱증발병궤제중적작용. 방법 노년Wister웅성대서수궤분위대조조화조모조,경과4주만성응격후조모성공.상규취혈청검측피질순함량,면역조화검측해마GR、MR표체. 결과 조모조대서종제2주개시섭식감소,체질량강저,청길활동감소,광장득분급당수섭입량균교대조조강저(P＜0.01).조모조대서혈피질순함량교대조조승고(P＜0.01).조모조해마신경원수량교대조조감소,이CA3구최위명현,이DG구무명현개변;해마CA3구GR양성세포수감소,MR양성세포수미견명현변화.결론 만성응격도치억욱노년대서HPA축공능문란,혈피질순함량승고,해마신경원수손,해마조직내GR표체량감소.만성응격도치적HPA축공능문란재억욱증발병궤제중구유중요작용.
Objective To observe the changes of behavior,blood cortisol level,glucocorticoid receptors (Grs) and mineralocorticoid receptors (MRs) in hippocampus area after four weeks of unpredictable chronic mild stress,and to investigate the probable role of hypothalamus-pituitary-adrenal (HPA) axis in the pathogenesis of depression in aged people.Methods Aged male Wister rats were randomly assigned to control group and model group.The model group received unpredictable mild stress,including food and water deprivation,restrain,tail clipping,forced swimming,white noise,cage titling and cage rotating for 4 weeks,while the control group was undisturbed unless routine feeding and cage changing.After 4 weeks of procedure,the behavior changes were assessed by sucrose intake test,open-field test and state evaluation,serum cortisol level was measured by chemiluminescent assay,the qualitation and quantitation of GRs and MRs in hippocampus area were evaluated by immunohistochemistry and Western blotting respectively.All data were analyzed by using t-test.Results Body weight,the grooming score,activities in openfield test,food intake and sucrose intake were decreased in model group as compared with control group after 2 weeks of chronic mild stress (all P＜0.01),suggesting the stress induced depressive-like behavior effects on aged rats.Serum cortisol level was elevated in model group as compared with control group after 4 weeks of chronic mild stress (P＜0.01).A decrease of the neurons was found in CA3 of hippocampus,but not in DG area.In CA3 area,GR positive neurons were decreased,but no significant decrease was found in MR positive neurons.Conclusions The chronic mild stress leading to depressive-like behavior effects in aged rats induces overall HPA axis dysfunction,elevation of serum cortisol level,impairment of hippocampus neurons and decrease of GR positive neurons.The HPA axis dysfunction induced by chronic mild stress may play an important role in the pathogenesis of depression.