老年抑郁大鼠血皮质醇与海马皮质醇受体的关系

Relationship between hippocampal cortisol receptors and serum cortisol in aged depression rats

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。

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 patbogenesis 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 tiffing 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 open- field 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 hippocalnpus, 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.