目的从行为学及分子水平比较皮质酮(CORT)与慢性不可预见性应激(CUMS)诱导的抑郁症模型的异同,为抑郁症发病机制研究及抗抑郁药物的筛选与评价模型提供一定的参考。方法将30只雄性C57BL/6小鼠随机分成对照组(Ctrl)、慢性不可预见应激组(CUMS)和皮质酮注射应激组(CORT)组,制作应激模型21d,期间每3d对小鼠进行称重。21d模型制作结束后,对小鼠进行行为学测试,并于第22天,通过眼眶取血收集动物血清,并用ELISA法测定血清皮质酮含量。眼眶取血后脱颈椎处死动物,取出动物的胸腺和脾脏进行称重,计算脏器指数;取出脑组织,置于液氮罐保存,尼氏(Nissl)染色法观察小鼠大脑海马区神经元损伤情况;采用Western blotting、RT-PCR方法测定抑郁症相关蛋白及基因的表达。结果与对照组相比,两种抑郁症模型组开场实验中的行为学指标均改变,强迫游泳和悬尾实验的累积不动时间显著升高。两个模型组的胸腺指数无明显变化,而CORT组的脾脏指数较对照组下降。CUMS和CORT组小鼠血清皮质酮含量高于对照组,CORT组与CUMS组相比有升高趋势,但差异无显著性。CUMS和CORT两种模型均使海马CA1、CA3和DG区神经元密度降低,CORT模型变化更明显。两模型组的促肾上腺素释放激素(CRH)的mRNA和蛋白的表达量均显著性增加,脑源性神经营养因子(BDNF)、磷酸化转录因子环磷腺苷反应元件结合蛋白(p-CREB)和磷酸化细胞外信号调节激酶(p-ERK)的蛋白表达水平均呈现明显地抑制,但CUMS和CORT两组之间差异无显著性。结论 CORT模型和CUMS模型均能成功构建抑郁症模型,且与下丘脑-垂体-肾上腺(HPA)轴紊乱有关,两种模型在小鼠海马结构改变及大脑BDNF-pCREB和ERK信号通路激活等方面差异无显著性。提示,CORT模型可用于抑郁症机制的研究及抗抑郁药的筛选与评价,尤其可用于以HPA轴功能紊乱所引起的抑郁症分子机制探讨。 Objective To compare the similarities and differences between depression model induced by cortisone (CORT) and chronic unpredictable stress (CUMS) from behavioral and molecular levels, and to provide some references for the study of the pathogenesis of depression and the selection and evaluation of antidepressants . Methods Thirty male C57BL / 6 mice were randomly divided into control group (Ctrl), chronic unpredictable stress group (CUMS) and cortisone injection stress group (CORT) Rats were weighed. After the 21d model was completed, the mice were subjected to behavioral testing. On the 22nd day, animal serum was collected by orbital bleeding and serum corticosterone level was measured by ELISA. Orbital vertebrae were removed from the eyes and sacrificed. The thymus and spleen of the animals were removed and weighed to calculate the organ index. The brain tissues were removed and stored in liquid nitrogen. Nissl staining was used to observe neurons in the hippocampus The expression of major depression-related proteins and genes was determined by Western blotting and RT-PCR. Results Compared with the control group, the behavioral indexes of the two models of depression model were changed during the opening experiment, and the cumulative immobility time of forced swimming and tail-suspension experiment was significantly increased. There was no significant change in the thymus index between the two model groups, while the spleen index of the CORT group was lower than that of the control group. The serum corticosterone levels in CUMS and CORT groups were higher than those in control group, and there was an increasing trend in CORT group and CUMS group, but the difference was not significant. Both CUMS and CORT decreased neuronal density in CA1, CA3 and DG of hippocampus, and the change of CORT model was more obvious. The mRNA and protein expression of adrenaline releasing hormone (CRH) were significantly increased in both model groups. The expressions of brain-derived neurotrophic factor (BDNF), phosphorylated transcription factor cyclic adenosine monophosphate response element binding protein (p-CREB ) And phosphorylated extracellular signal-regulated kinase (p-ERK) protein expression levels were significantly inhibited, but there was no significant difference between the CUMS and CORT groups. Conclusion Both CORT model and CUMS model can successfully construct depression model, which is related to disturbance of hypothalamus-pituitary-adrenal (HPA) axis. Both of them are involved in the structural changes of hippocampus and the activation of BDNF-pCREB and ERK signaling pathways No significant difference. It is suggested that the CORT model can be used to study the mechanism of depression and the screening and evaluation of antidepressants. It can be used to explore the molecular mechanism of depression caused by HPA axis dysfunction.