本文選題：抑郁癥　切入點(diǎn)：動物模型　出處：《中國病理生理雜志》2017年06期

【摘要】：目的:利用腦內(nèi)神經(jīng)遞質(zhì)對的拮抗關(guān)系建立新型抑郁癥大鼠模型。方法:通過海馬微量注射低、中、高劑量(1、2和4 g/L)的多巴胺D1受體拮抗劑SCH23390造模后,利用糖水消耗實(shí)驗(yàn)、曠場實(shí)驗(yàn)及新環(huán)境進(jìn)食抑制實(shí)驗(yàn)等評價(jià)動物抑郁行為表現(xiàn),以篩選出最佳造模藥物劑量。應(yīng)用最佳造模劑量造模后,連續(xù)觀察,2周后對該模型進(jìn)行評價(jià),通過行為學(xué)測試評價(jià)該模型癥狀的穩(wěn)定性,采用ELISA法測定腦脊液中IL-1β和TNF-α的含量評價(jià)該模型的安全性,采用高效液相色譜-質(zhì)譜技術(shù)(HPLC-MS)定量檢測大腦皮層和海馬中5-羥色胺(5-HT)、去甲腎上腺素(NE)、多巴胺(DA)、乙酰膽堿(ACh)、谷氨酸(Glu)和γ-氨基丁酸(GABA)等神經(jīng)遞質(zhì)的水平,以此評價(jià)該模型腦內(nèi)神經(jīng)遞質(zhì)失衡的病理特征。結(jié)果:造模結(jié)束后,各劑量造模組大鼠體重、糖水偏愛率、水平運(yùn)動得分和垂直運(yùn)動得分均明顯降低,新環(huán)境進(jìn)食抑制時(shí)間增長,表現(xiàn)為典型的抑郁樣行為,以中劑量造模組大鼠的抑郁行為表現(xiàn)最為顯著;造模后2周,與正常對照組相比,中劑量造模組大鼠的體重、糖水偏愛率、水平運(yùn)動得分和垂直運(yùn)動得分均明顯降低(P0.01),新環(huán)境進(jìn)食抑制時(shí)間增長(P0.05)。正常對照組、空白對照組和中劑量造模組大鼠腦脊液中IL-1β和TNF-α的含量均無顯著變化,說明該模型未造成明顯炎性損傷,造模方法安全。與空白對照組相比,中劑量造模組大鼠左側(cè)海馬5-HT、NE和Glu含量均顯著升高(P0.01),DA和ACh含量均呈降低趨勢;右側(cè)海馬5-HT、NE和Glu含量均顯著升高(P0.05),DA和ACh含量均呈降低趨勢;大腦皮層Glu含量顯著升高(P0.05),5-HT和NE含量均呈升高趨勢,DA和ACh含量均呈降低趨勢,說明該模型基本符合抑郁癥腦內(nèi)神經(jīng)遞質(zhì)失衡的病理特征。結(jié)論:此方法可成功復(fù)制抑郁癥大鼠模型,該模型具有癥狀典型而持久、成�？焖�、操作簡便安全等特點(diǎn),較合適的造模藥物劑量為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- 偽 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- 偽 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).
【作者單位】： 北京中醫(yī)藥大學(xué);
【基金】：國家重點(diǎn)基礎(chǔ)研究發(fā)展計(jì)劃(973計(jì)劃)課題(No.2012CB518602)
【分類號】：R-332;R749.4

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 李淑云;簡易大鼠灌胃器的制作[J];錦州醫(yī)學(xué)院學(xué)報(bào);2001年04期

2 孫同柱,付小兵,翁立新,梁雪梅,陳偉;介紹一種簡易的大鼠保定方法[J];上海實(shí)驗(yàn)動物科學(xué);2004年01期

3 周劍鋒,李娜,袁發(fā)煥,張耀全;腎間質(zhì)纖維化模型建立中大鼠行為改變的研究[J];中國行為醫(yī)學(xué)科學(xué);2005年04期

4 符路娣;蔡海云;;介紹一種簡便的大鼠灌胃方法[J];中獸醫(yī)學(xué)雜志;2006年03期

5 劉海燕;;灌注固定大鼠的技術(shù)操作及常見問題[J];齊齊哈爾醫(yī)學(xué)院學(xué)報(bào);2006年11期

6 馮雪建;盧占軍;高登慧;;大鼠灌胃給藥方法的研究[J];實(shí)驗(yàn)動物科學(xué)與管理;2006年04期

7 梁秀蘭;阮祥燕;蔣輝;王迎;;SD大鼠絕經(jīng)模型建立的研究[J];醫(yī)學(xué)綜述;2010年09期

8 楊光瑜;周繼紅;尹志勇;張岫竹;張良;劉大維;;低頻共振對大鼠生理功能影響研究[J];醫(yī)用生物力學(xué);2011年02期

9 郭恒怡,劉探娥,曹青,孫瑛,蔡英年,鄧希賢,陳華粹;缺氧敏感性不同的兩種大鼠心、肺組織腎上腺素類受體的比較[J];生理科學(xué);1986年05期

10 長瀨墨 ,左謙益;一種缺乏白蛋白血癥的動物模型——白蛋白缺乏的突變大鼠[J];微生物學(xué)免疫學(xué)譯刊;1987年S1期

相關(guān)會議論文 前10條

1 櫖蒲生;王日宏;杝灄生;，

本文編號：1703920