發(fā)布時(shí)間：2018-04-08 08:08

  本文選題：抑郁癥　切入點(diǎn)：模型　出處：《中國(guó)比較醫(yī)學(xué)雜志》2017年04期

【摘要】：目的海馬內(nèi)微量注射K252a,研究其對(duì)大鼠行為學(xué)及抑郁樣經(jīng)典指標(biāo)的影響,擬建立一種新型抑郁癥動(dòng)物模型。方法 SD大鼠隨機(jī)分為5組,即空白對(duì)照組、假手術(shù)組、慢性應(yīng)激抑郁模型組、海馬內(nèi)微量注射K252a組、海馬內(nèi)微量注射K252a聯(lián)合慢性應(yīng)激組。采用Open field實(shí)驗(yàn)、糖水消耗實(shí)驗(yàn)、Morris水迷宮測(cè)定大鼠行為學(xué)的影響,ELISA法檢測(cè)大鼠血清單胺遞質(zhì)含量的變化,放射免疫法觀察大鼠血漿CRH、ACTH、CORT含量的變化,Western blotting觀察大鼠海馬BDNF、CREB、ERK1/2、BCL-2蛋白表達(dá)的變化。結(jié)果與空白對(duì)照組比較,CUMS組大鼠的活動(dòng)量、糖水消耗量、學(xué)習(xí)記憶能力顯著降低(P0.05或P0.01),HPA軸功能亢進(jìn)(P0.01),血清單胺遞質(zhì)水平降低(P0.01),BDNF、CREB、ERK1/2、BCL-2的表達(dá)下調(diào)(P0.01或P0.05),而DMSO組上述指標(biāo)差異無(wú)統(tǒng)計(jì)學(xué)意義;與DMSO比較,K252a組、K252a+CUMS組活動(dòng)量、糖水消耗量、學(xué)習(xí)記憶能力顯著下降(P0.01或P0.05),血清單胺遞質(zhì)水平下降(P0.01或P0.05),HPA軸功能顯著上升(P0.01或P0.05),海馬BDNF、CREB、ERK1/2、BCL-2的表達(dá)顯著下降(P0.01或P0.05);與CUMS組比較,K252a組、K252a+CUMS組大鼠上述指標(biāo)差異無(wú)顯著性;與K252a組比較,K252a+CUMS組大鼠上述指標(biāo)差異無(wú)顯著性。結(jié)論從行為學(xué)、血液學(xué)、分子生物學(xué)的不同角度分析表明,此模型與經(jīng)典的慢性應(yīng)激抑郁模型在表面效度、結(jié)構(gòu)效度、功能效度上具有極大的相似性,可為病因研究和抗抑郁藥物篩選提供一個(gè)可供選擇的研究技術(shù)平臺(tái)。
[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.
【作者單位】： 湖南中醫(yī)藥大學(xué);湖南省中藥粉體與創(chuàng)新藥物省部共建國(guó)家重點(diǎn)實(shí)驗(yàn)室培育基地;湖南省腫瘤醫(yī)院;湖南中醫(yī)藥大學(xué)第一附屬醫(yī)院;
【基金】：國(guó)家自然科學(xué)基金青年項(xiàng)目(81403387) 湖南省教育廳一般項(xiàng)目(14C0862;15C1038) 湖南省科技廳重點(diǎn)項(xiàng)目(2015DK3003) 中醫(yī)內(nèi)科學(xué)省部共建教育部重點(diǎn)實(shí)驗(yàn)室開放基金(ZYNK201503)
【分類號(hào)】：R749.4

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