精神分裂癥動(dòng)物模型的拓展及在相關(guān)基因和藥物篩選中的應(yīng)用
發(fā)布時(shí)間:2018-12-20 07:34
【摘要】:基于本研究組此前建立的以谷氨酸N-甲基-D-天門冬氨酸受體(NMDA)非競爭性拮抗劑MK801(5 甲基二氫二苯并環(huán)庚烯亞氨馬來酸,地卓西平馬來酸鹽)誘導(dǎo)的精神分裂癥動(dòng)物模型,我們探索了類似精神分裂癥的模型小鼠在認(rèn)知、探索能力和痛覺感應(yīng)等方面的表現(xiàn)。實(shí)驗(yàn)結(jié)果表明:模型小鼠在洞板試驗(yàn)中探洞次數(shù)顯著下降,甩尾時(shí)間也相對延長,以常用的非典型性抗精神病藥物利培酮和奧氮平進(jìn)行處理,可以抑制這兩種效果,進(jìn)一步證明了該模型的擬真度。在將該模型與反義核酸技術(shù)結(jié)合后,作者構(gòu)建了一個(gè)篩選精神分裂癥相關(guān)基因的技術(shù)平臺(tái),并以此平臺(tái)考察了5 個(gè)候選基因,其中有2 個(gè)基因所對應(yīng)的實(shí)驗(yàn)組在曠場行為及異?贪逍詣(dòng)作方面與對照組差異顯著,可認(rèn)為與精神分裂癥相關(guān)。以神經(jīng)肽類藥物GNTI(5-胍基吶曲吲哚)作用于該模型,也可以部分抑制曠場移動(dòng)過快等類似精神分裂癥的癥狀,表明該藥物具有一定的抗精神分裂癥作用,并證明了該模型用于新藥篩選的可行性。
[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.
【學(xué)位授予單位】:中國科學(xué)院研究生院(上海生命科學(xué)研究院)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2005
【分類號】:R-332
本文編號: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.
【學(xué)位授予單位】:中國科學(xué)院研究生院(上海生命科學(xué)研究院)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2005
【分類號】:R-332
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相關(guān)期刊論文 前2條
1 金玫蕾,莫韞,劉留,郭寧,謝青蓮,林楨,王星,李葆明,趙國屏,景乃禾,于雷;篩選神經(jīng)系統(tǒng)基因功能的行為學(xué)檢測平臺(tái)的探索[J];生理學(xué)報(bào);2001年04期
2 吳金華,鄒洪,于軍,周雪東,謝青蓮,金玫蕾;用不同實(shí)驗(yàn)小鼠品系建立精神分裂癥的動(dòng)物模型[J];生理學(xué)報(bào);2003年04期
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