精神分裂症动物模型的拓展及在相关基因和药物筛选中的应用
发布时间：2018-12-20 07:34
【摘要】：基于本研究组此前建立的以谷氨酸N-甲基-D-天门冬氨酸受体(NMDA)非竞争性拮抗剂MK801(5 甲基二氢二苯并环庚烯亚氨马来酸,地卓西平马来酸盐)诱导的精神分裂症动物模型,我们探索了类似精神分裂症的模型小鼠在认知、探索能力和痛觉感应等方面的表现。实验结果表明:模型小鼠在洞板试验中探洞次数显著下降,甩尾时间也相对延长,以常用的非典型性抗精神病药物利培酮和奥氮平进行处理,可以抑制这两种效果,进一步证明了该模型的拟真度。在将该模型与反义核酸技术结合后,作者构建了一个筛选精神分裂症相关基因的技术平台,并以此平台考察了5 个候选基因,其中有2 个基因所对应的实验组在旷场行为及异常刻板性动作方面与对照组差异显著,可认为与精神分裂症相关。以神经肽类药物GNTI(5-胍基呐曲吲哚)作用于该模型,也可以部分抑制旷场移动过快等类似精神分裂症的症状,表明该药物具有一定的抗精神分裂症作用,并证明了该模型用于新药筛选的可行性。
[Abstract]:Based on the previously established N-methyl-D-aspartate glutamate receptor (NMDA) non-competitive antagonist MK801 (5-methyldihydrodihydrobenzo-cycloheptene maleic acid), The animal model of schizophrenia induced by didroxepine maleate) was established. We explored the cognitive, exploratory and pain-sensing abilities of the model mice similar to schizophrenia. The results showed that the number of holes was significantly decreased and the tail flick time was prolonged in the model mice. Treatment with risperidone and olanzapine, a common antipsychotic drug, could inhibit these two effects. The quasi-trueness of the model is further proved. After combining the model with antisense nucleic acid technology, the authors constructed a technique platform for screening schizophrenia related genes and examined five candidate genes. There were significant differences in open field behavior and abnormal stereotype between the two genes in the experimental group and the control group, which could be considered to be related to schizophrenia. The effects of neuropeptide drug GNTI (5-guanidindoline) on the model also partly inhibited the symptoms of schizophrenia such as over-fast open field movement, which indicated that the drug had a certain anti-schizophrenia effect. The feasibility of applying the model to new drug screening is proved.
【学位授予单位】：中国科学院研究生院（上海生命科学研究院）
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R-332
本文编号：2387658
[Abstract]:Based on the previously established N-methyl-D-aspartate glutamate receptor (NMDA) non-competitive antagonist MK801 (5-methyldihydrodihydrobenzo-cycloheptene maleic acid), The animal model of schizophrenia induced by didroxepine maleate) was established. We explored the cognitive, exploratory and pain-sensing abilities of the model mice similar to schizophrenia. The results showed that the number of holes was significantly decreased and the tail flick time was prolonged in the model mice. Treatment with risperidone and olanzapine, a common antipsychotic drug, could inhibit these two effects. The quasi-trueness of the model is further proved. After combining the model with antisense nucleic acid technology, the authors constructed a technique platform for screening schizophrenia related genes and examined five candidate genes. There were significant differences in open field behavior and abnormal stereotype between the two genes in the experimental group and the control group, which could be considered to be related to schizophrenia. The effects of neuropeptide drug GNTI (5-guanidindoline) on the model also partly inhibited the symptoms of schizophrenia such as over-fast open field movement, which indicated that the drug had a certain anti-schizophrenia effect. The feasibility of applying the model to new drug screening is proved.
【学位授予单位】：中国科学院研究生院（上海生命科学研究院）
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R-332
【参考文献】
相关期刊论文 前2条
1 金玫蕾,莫韫,刘留,郭宁,谢青莲,林桢,王星,李葆明,赵国屏,景乃禾,于雷;筛选神经系统基因功能的行为学检测平台的探索[J];生理学报;2001年04期
2 吴金华,邹洪,于军,周雪东,谢青莲,金玫蕾;用不同实验小鼠品系建立精神分裂症的动物模型[J];生理学报;2003年04期
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