皮质酮与慢性不可预见性应激诱导的两种抑郁症模型比较

发布时间：2017-12-31 18:24

本文关键词：皮质酮与慢性不可预见性应激诱导的两种抑郁症模型比较　出处：《解剖学报》2017年03期 　论文类型：期刊论文

【摘要】：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。
[Abstract]:Objective to compare the behavioral and molecular differences between corticosterone (Cort) and chronic unpredictable stress (CUMS) induced depression model. Methods 30 male C57BL / 6 mice were randomly divided into control group (Ctrl). Chronic unpredictable stress group (CUMS) and corticosterone injection stress group (Cort) group, the stress model was made for 21 days, during which mice were weighed every 3 days. On the 22nd day, the serum was collected from the mice, and the content of corticosterone in the serum was determined by ELISA method. The animals were killed after the blood was taken from the orbit. The thymus and spleen of the animal were weighed and the viscera index was calculated. The brain tissue was taken out and stored in a liquid nitrogen tank. The neuronal damage in the hippocampal area of mice was observed by Nissli staining. Western blotting RT-PCR was used to detect the expression of depression related proteins and genes, and the results were compared with those in the control group. The behavioral indexes in the open field test of the two kinds of depression model groups were all changed, the cumulative immobility time of forced swimming and tail suspension test was significantly increased, but the thymus index of the two model groups had no significant change. However, the spleen index in CORT group was lower than that in control group. The serum corticosterone content in CUMS and CORT group was higher than that in Cort group and CUMS group. However, there was no significant difference between the two models. CUMS and CORT reduced the density of neurons in hippocampal CA1, CA3 and DG regions. The changes of CORT model were more obvious. The expression of mRNA and protein were significantly increased in the two model groups, and brain-derived neurotrophic factor (BDNF). The expression levels of phosphorylated transcription factor cyclic adenosine responsive element binding protein (p-CREB) and phosphorylated extracellular signal-regulated kinase p-ERK (p-ERK) were significantly inhibited. But there was no significant difference between CUMS and CORT. Conclusion both CORT model and CUMS model can construct depression model successfully. And associated with hypothalamus-pituitary-adrenal gland HPA axis disorder. There was no significant difference between the two models in the changes of hippocampal structure and the activation of BDNF-pCREB and ERK signaling pathways in the brain of mice. CORT model can be used to study the mechanism of depression and to screen and evaluate antidepressants, especially to explore the molecular mechanism of depression caused by HPA axis dysfunction.
【作者单位】：中国药科大学江苏省中药评价与转化重点实验室;中国药科大学天然药物活性组分与药效国家重点实验室;中国科学院藏药研究重点实验室;青海省藏药药理学和安全性评价研究重点实验室;
【基金】：中国科学院百人计划(Y229461211) 2017年中华医学会-欧莱雅中国人健康皮肤/毛发研究项目(S2017140917)
【分类号】：R-332;R749.4
【正文快照】： 评价研究重点实验室,西宁810001)抑郁症是一种情感性精神障碍,主要症状为心境抑郁、兴趣丧失、睡眠紊乱、食欲寡淡、活动减少、注意力下降以及自杀倾向等[1],已经成为一种临床常见疾病。抑郁症发病机制复杂,涉及遗传、人格和社会环境等众多因素,抑郁症发病往往伴随着单胺类神

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