本文關(guān)鍵詞：皮質(zhì)酮與慢性不可預(yù)見性應(yīng)激誘導(dǎo)的兩種抑郁癥模型比較　出處：《解剖學(xué)報(bào)》2017年03期 　論文類型：期刊論文

  更多相關(guān)文章： 抑郁癥 慢性不可預(yù)見性應(yīng)激 皮質(zhì)酮 免疫印跡法 小鼠

【摘要】：目的從行為學(xué)及分子水平比較皮質(zhì)酮(CORT)與慢性不可預(yù)見性應(yīng)激(CUMS)誘導(dǎo)的抑郁癥模型的異同,為抑郁癥發(fā)病機(jī)制研究及抗抑郁藥物的篩選與評(píng)價(jià)模型提供一定的參考。方法將30只雄性C57BL/6小鼠隨機(jī)分成對(duì)照組(Ctrl)、慢性不可預(yù)見應(yīng)激組(CUMS)和皮質(zhì)酮注射應(yīng)激組(CORT)組,制作應(yīng)激模型21d,期間每3d對(duì)小鼠進(jìn)行稱重。21d模型制作結(jié)束后,對(duì)小鼠進(jìn)行行為學(xué)測(cè)試,并于第22天,通過眼眶取血收集動(dòng)物血清,并用ELISA法測(cè)定血清皮質(zhì)酮含量。眼眶取血后脫頸椎處死動(dòng)物,取出動(dòng)物的胸腺和脾臟進(jìn)行稱重,計(jì)算臟器指數(shù);取出腦組織,置于液氮罐保存,尼氏(Nissl)染色法觀察小鼠大腦海馬區(qū)神經(jīng)元損傷情況;采用Western blotting、RT-PCR方法測(cè)定抑郁癥相關(guān)蛋白及基因的表達(dá)。結(jié)果與對(duì)照組相比,兩種抑郁癥模型組開場(chǎng)實(shí)驗(yàn)中的行為學(xué)指標(biāo)均改變,強(qiáng)迫游泳和懸尾實(shí)驗(yàn)的累積不動(dòng)時(shí)間顯著升高。兩個(gè)模型組的胸腺指數(shù)無明顯變化,而CORT組的脾臟指數(shù)較對(duì)照組下降。CUMS和CORT組小鼠血清皮質(zhì)酮含量高于對(duì)照組,CORT組與CUMS組相比有升高趨勢(shì),但差異無顯著性。CUMS和CORT兩種模型均使海馬CA1、CA3和DG區(qū)神經(jīng)元密度降低,CORT模型變化更明顯。兩模型組的促腎上腺素釋放激素(CRH)的mRNA和蛋白的表達(dá)量均顯著性增加,腦源性神經(jīng)營養(yǎng)因子(BDNF)、磷酸化轉(zhuǎn)錄因子環(huán)磷腺苷反應(yīng)元件結(jié)合蛋白(p-CREB)和磷酸化細(xì)胞外信號(hào)調(diào)節(jié)激酶(p-ERK)的蛋白表達(dá)水平均呈現(xiàn)明顯地抑制,但CUMS和CORT兩組之間差異無顯著性。結(jié)論 CORT模型和CUMS模型均能成功構(gòu)建抑郁癥模型,且與下丘腦-垂體-腎上腺(HPA)軸紊亂有關(guān),兩種模型在小鼠海馬結(jié)構(gòu)改變及大腦BDNF-pCREB和ERK信號(hào)通路激活等方面差異無顯著性。提示,CORT模型可用于抑郁癥機(jī)制的研究及抗抑郁藥的篩選與評(píng)價(jià),尤其可用于以HPA軸功能紊亂所引起的抑郁癥分子機(jī)制探討。
[Abstract]:Objective to compare the behavioral and molecular differences between corticosterone (Cort) and chronic unpredictable stress (CUMS) induced depression model. Methods 30 male C57BL / 6 mice were randomly divided into control group (Ctrl). Chronic unpredictable stress group (CUMS) and corticosterone injection stress group (Cort) group, the stress model was made for 21 days, during which mice were weighed every 3 days. On the 22nd day, the serum was collected from the mice, and the content of corticosterone in the serum was determined by ELISA method. The animals were killed after the blood was taken from the orbit. The thymus and spleen of the animal were weighed and the viscera index was calculated. The brain tissue was taken out and stored in a liquid nitrogen tank. The neuronal damage in the hippocampal area of mice was observed by Nissli staining. Western blotting RT-PCR was used to detect the expression of depression related proteins and genes, and the results were compared with those in the control group. The behavioral indexes in the open field test of the two kinds of depression model groups were all changed, the cumulative immobility time of forced swimming and tail suspension test was significantly increased, but the thymus index of the two model groups had no significant change. However, the spleen index in CORT group was lower than that in control group. The serum corticosterone content in CUMS and CORT group was higher than that in Cort group and CUMS group. However, there was no significant difference between the two models. CUMS and CORT reduced the density of neurons in hippocampal CA1, CA3 and DG regions. The changes of CORT model were more obvious. The expression of mRNA and protein were significantly increased in the two model groups, and brain-derived neurotrophic factor (BDNF). The expression levels of phosphorylated transcription factor cyclic adenosine responsive element binding protein (p-CREB) and phosphorylated extracellular signal-regulated kinase p-ERK (p-ERK) were significantly inhibited. But there was no significant difference between CUMS and CORT. Conclusion both CORT model and CUMS model can construct depression model successfully. And associated with hypothalamus-pituitary-adrenal gland HPA axis disorder. There was no significant difference between the two models in the changes of hippocampal structure and the activation of BDNF-pCREB and ERK signaling pathways in the brain of mice. CORT model can be used to study the mechanism of depression and to screen and evaluate antidepressants, especially to explore the molecular mechanism of depression caused by HPA axis dysfunction.
【作者單位】： 中國藥科大學(xué)江蘇省中藥評(píng)價(jià)與轉(zhuǎn)化重點(diǎn)實(shí)驗(yàn)室;中國藥科大學(xué)天然藥物活性組分與藥效國家重點(diǎn)實(shí)驗(yàn)室;中國科學(xué)院藏藥研究重點(diǎn)實(shí)驗(yàn)室;青海省藏藥藥理學(xué)和安全性評(píng)價(jià)研究重點(diǎn)實(shí)驗(yàn)室;
【基金】：中國科學(xué)院百人計(jì)劃(Y229461211) 2017年中華醫(yī)學(xué)會(huì)-歐萊雅中國人健康皮膚/毛發(fā)研究項(xiàng)目(S2017140917)
【分類號(hào)】：R-332;R749.4
【正文快照】： 評(píng)價(jià)研究重點(diǎn)實(shí)驗(yàn)室,西寧810001)抑郁癥是一種情感性精神障礙,主要癥狀為心境抑郁、興趣喪失、睡眠紊亂、食欲寡淡、活動(dòng)減少、注意力下降以及自殺傾向等[1],已經(jīng)成為一種臨床常見疾病。抑郁癥發(fā)病機(jī)制復(fù)雜,涉及遺傳、人格和社會(huì)環(huán)境等眾多因素,抑郁癥發(fā)病往往伴隨著單胺類神

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