基于脑内神经递质对的拮抗关系建立新型抑郁症大鼠模型的实验研究

发布时间：2018-04-03 06:04

本文选题：抑郁症　切入点：动物模型　出处：《中国病理生理杂志》2017年06期

【摘要】：目的:利用脑内神经递质对的拮抗关系建立新型抑郁症大鼠模型。方法:通过海马微量注射低、中、高剂量(1、2和4 g/L)的多巴胺D1受体拮抗剂SCH23390造模后,利用糖水消耗实验、旷场实验及新环境进食抑制实验等评价动物抑郁行为表现,以筛选出最佳造模药物剂量。应用最佳造模剂量造模后,连续观察,2周后对该模型进行评价,通过行为学测试评价该模型症状的稳定性,采用ELISA法测定脑脊液中IL-1β和TNF-α的含量评价该模型的安全性,采用高效液相色谱-质谱技术(HPLC-MS)定量检测大脑皮层和海马中5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)、乙酰胆碱(ACh)、谷氨酸(Glu)和γ-氨基丁酸(GABA)等神经递质的水平,以此评价该模型脑内神经递质失衡的病理特征。结果:造模结束后,各剂量造模组大鼠体重、糖水偏爱率、水平运动得分和垂直运动得分均明显降低,新环境进食抑制时间增长,表现为典型的抑郁样行为,以中剂量造模组大鼠的抑郁行为表现最为显著;造模后2周,与正常对照组相比,中剂量造模组大鼠的体重、糖水偏爱率、水平运动得分和垂直运动得分均明显降低(P0.01),新环境进食抑制时间增长(P0.05)。正常对照组、空白对照组和中剂量造模组大鼠脑脊液中IL-1β和TNF-α的含量均无显著变化,说明该模型未造成明显炎性损伤,造模方法安全。与空白对照组相比,中剂量造模组大鼠左侧海马5-HT、NE和Glu含量均显著升高(P0.01),DA和ACh含量均呈降低趋势;右侧海马5-HT、NE和Glu含量均显著升高(P0.05),DA和ACh含量均呈降低趋势;大脑皮层Glu含量显著升高(P0.05),5-HT和NE含量均呈升高趋势,DA和ACh含量均呈降低趋势,说明该模型基本符合抑郁症脑内神经递质失衡的病理特征。结论:此方法可成功复制抑郁症大鼠模型,该模型具有症状典型而持久、成模快速、操作简便安全等特点,较合适的造模药物剂量为2 g/L。
[Abstract]:Aim: to establish a new type of depression rat model by using the antagonistic relationship of neurotransmitter pairs in the brain.Methods: after microinjection of low, middle and high doses of dopamine D1 receptor antagonist SCH23390 into hippocampus, the depressive behavior of animals was evaluated by sugar water consumption test, open field test and new environment food inhibition test.In order to screen the best drug dosage.The model was evaluated after two weeks of continuous observation. The stability of the model symptoms was evaluated by behavioral test. The safety of the model was evaluated by ELISA method. The contents of IL-1 尾 and TNF- 伪 in cerebrospinal fluid (CSF) were determined by ELISA method.High performance liquid chromatography-mass spectrometry (HPLC-MS) was used to quantitatively detect the levels of neurotransmitters such as 5-hydroxytryptamine, noradrenaline, dopamine, acetylcholine, acetylcholine, glutamate and gamma-aminobutyric acid (GABA) in the cerebral cortex and hippocampus.The pathological characteristics of neurotransmitter imbalance in the brain of the model were evaluated.Results: the body weight, sugar water preference rate, horizontal exercise score and vertical exercise score of rats in each dose of model group were significantly decreased after model making, and the time of food intake inhibition in new environment was increased, which showed typical depressive behavior.The depression behavior of the rats in the middle dose model group was the most significant, and the weight and sugar water preference rate of the middle dose model group was higher than that of the normal control group at 2 weeks after the model was made.The scores of horizontal exercise and vertical exercise were significantly decreased (P 0.01), and the time of eating inhibition in new environment was increased (P 0.05).The contents of IL-1 尾 and TNF- 伪 in cerebrospinal fluid of normal control group, blank control group and middle dose model group were not significantly changed, indicating that the model did not cause obvious inflammatory injury, and the method of modeling was safe.Compared with the blank control group, the contents of 5-HT NE and Glu in the left hippocampus of the middle dose model group were significantly increased, the contents of DA and ACh in the left hippocampus were significantly increased, and the contents of 5-HT ne and Glu in the right hippocampus were significantly higher than those in the control group.The contents of 5-HT and NE in cerebral cortex increased significantly, and the contents of DA and ACh decreased, indicating that the model basically accords with the pathological characteristics of neurotransmitter imbalance in depression.Conclusion: this method can successfully replicate the rat model of depression. The model has the characteristics of typical and lasting symptoms, rapid model formation, simple and safe operation, etc. The more suitable drug dosage is 2 g 路L ~ (-1).
【作者单位】：北京中医药大学;
【基金】：国家重点基础研究发展计划(973计划)课题(No.2012CB518602)
【分类号】：R-332;R749.4

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