海马内微量注射K252a对大鼠行为学及抑郁样经典指标的影响

发布时间：2018-04-08 08:08

本文选题：抑郁症　切入点：模型　出处：《中国比较医学杂志》2017年04期

【摘要】：目的海马内微量注射K252a,研究其对大鼠行为学及抑郁样经典指标的影响,拟建立一种新型抑郁症动物模型。方法 SD大鼠随机分为5组,即空白对照组、假手术组、慢性应激抑郁模型组、海马内微量注射K252a组、海马内微量注射K252a联合慢性应激组。采用Open field实验、糖水消耗实验、Morris水迷宫测定大鼠行为学的影响,ELISA法检测大鼠血清单胺递质含量的变化,放射免疫法观察大鼠血浆CRH、ACTH、CORT含量的变化,Western blotting观察大鼠海马BDNF、CREB、ERK1/2、BCL-2蛋白表达的变化。结果与空白对照组比较,CUMS组大鼠的活动量、糖水消耗量、学习记忆能力显著降低(P0.05或P0.01),HPA轴功能亢进(P0.01),血清单胺递质水平降低(P0.01),BDNF、CREB、ERK1/2、BCL-2的表达下调(P0.01或P0.05),而DMSO组上述指标差异无统计学意义;与DMSO比较,K252a组、K252a+CUMS组活动量、糖水消耗量、学习记忆能力显著下降(P0.01或P0.05),血清单胺递质水平下降(P0.01或P0.05),HPA轴功能显著上升(P0.01或P0.05),海马BDNF、CREB、ERK1/2、BCL-2的表达显著下降(P0.01或P0.05);与CUMS组比较,K252a组、K252a+CUMS组大鼠上述指标差异无显著性;与K252a组比较,K252a+CUMS组大鼠上述指标差异无显著性。结论从行为学、血液学、分子生物学的不同角度分析表明,此模型与经典的慢性应激抑郁模型在表面效度、结构效度、功能效度上具有极大的相似性,可为病因研究和抗抑郁药物筛选提供一个可供选择的研究技术平台。
[Abstract]:Objective to study the effect of intrahippocampal microinjection of K252a on behavioral and depression-like classic indexes in rats and to establish a new type of depression animal model.Methods SD rats were randomly divided into 5 groups: blank control group, sham operation group, chronic stress depression model group, intrahippocampal microinjection K252a group, intrahippocampal microinjection K252a combined with chronic stress group.Open field test and Morris water maze test were used to determine the behavior of rats. The changes of serum monoamine transmitters in rats were detected by Elisa.Radioimmunoassay was used to observe the changes of plasma CRHN-ACTHH-CORT in rats and the expression of BDNF-CREBERK1 / 2 BCL-2 protein in rat hippocampus was observed by Western blotting.Results compared with the blank control group, the activity and sugar water consumption of rats in CUMS group were compared.The ability of learning and memory decreased significantly (P0.01 or P0.05), the level of serum monoamine transmitters decreased P0.01 or P0.05, the function of HPA axis increased significantly (P0.01 or P0.05), and the expression of BCL-2 in hippocampal BDNF CREBEBERK1 / 2 + BCL-2 decreased significantly (P0.01 or P0.05), but there was no significant difference between K252a group and K252a group (P0.01 or P0.05).There was no significant difference between K252a CUMS group and K252a group.Conclusion from different angles of behavior, hematology and molecular biology, this model is similar to the classical chronic stress depression model in surface validity, structural validity and functional validity.It can provide an alternative research technology platform for etiology research and antidepressant drug screening.
【作者单位】：湖南中医药大学;湖南省中药粉体与创新药物省部共建国家重点实验室培育基地;湖南省肿瘤医院;湖南中医药大学第一附属医院;
【基金】：国家自然科学基金青年项目(81403387) 湖南省教育厅一般项目(14C0862;15C1038) 湖南省科技厅重点项目(2015DK3003) 中医内科学省部共建教育部重点实验室开放基金(ZYNK201503)
【分类号】：R749.4

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