抑郁模型大鼠海馬組織中內(nèi)質(zhì)網(wǎng)應(yīng)激調(diào)控因子的表達(dá)及β-細(xì)辛醚的干預(yù)作用
本文選題:β-細(xì)辛醚 + 抑郁 ; 參考:《中國實驗方劑學(xué)雜志》2017年08期
【摘要】:目的:研究抑郁模型大鼠海馬組織中內(nèi)質(zhì)網(wǎng)應(yīng)激調(diào)控因子的表達(dá)及β-細(xì)辛醚的干預(yù)作用,并探討其相關(guān)的作用機(jī)制。方法:建立慢性輕度不可預(yù)見性應(yīng)激刺激(CUMS)大鼠模型,將100只大鼠隨機(jī)分為5組,分別為正常組,模型組,氟西汀組(10 mg·kg-1),β-細(xì)辛醚低劑量組(25 mg·kg-1)和高劑量組(50 mg·kg-1),每組20只,從造模第8天開始每天灌胃1次給藥,連續(xù)21 d。于實驗的第0天和第29天進(jìn)行曠場實驗;采用Nissl染色法觀察各組大鼠海馬組織神經(jīng)元尼氏體的變化;實時熒光定量PCR(Real-time PCR)技術(shù)檢測各組大鼠海馬組織蛋白激酶R樣內(nèi)質(zhì)網(wǎng)激酶(PERK),CCAAT/增強(qiáng)子結(jié)合蛋白同源蛋白(CHOP),鈣網(wǎng)蛋白(CRT)mRNA表達(dá)情況;蛋白質(zhì)免疫印跡(Western blot)技術(shù)檢測各組大鼠海馬組織PERK,CHOP,CRT蛋白表達(dá)。結(jié)果:經(jīng)28 d慢性不可預(yù)見性溫和刺激后,模型組大鼠與正常組大鼠比較,水平運(yùn)動和垂直運(yùn)動得分明顯減少(P0.05);β-細(xì)辛醚低、高劑量組和氟西汀組大鼠與模型組比較,水平運(yùn)動和垂直運(yùn)動得分明顯增加(P0.05)。尼氏染色結(jié)果顯示,模型組大鼠海馬組織神經(jīng)元細(xì)胞漿著色變淺,尼氏小體顆粒明顯減少;β-細(xì)辛醚低、高劑量組大鼠海馬區(qū)神經(jīng)元形態(tài)相對較好,尼氏小體顆粒較模型組增多。模型組與正常組大鼠比較,PERK,CHOP,CRT mRNA表達(dá)上調(diào)(P0.05),與模型組比較,β-細(xì)辛醚低、高劑量組和氟西汀組中PERK,CHOP,CRT mRNA表達(dá)明顯下調(diào)(P0.05)。與正常組比較,模型組大鼠PERK,CHOP,CRT蛋白表達(dá)均明顯升高(P0.05);與模型組大鼠比較,氟西汀組、β-細(xì)辛醚低、高劑量組PERK,CHOP,CRT蛋白表達(dá)明顯減少(P0.05)。結(jié)論:β-細(xì)辛醚可能是通過調(diào)節(jié)海馬內(nèi)質(zhì)網(wǎng)功能發(fā)揮抗抑郁作用。
[Abstract]:Aim: to investigate the expression of endoplasmic reticulum (ER) stress regulatory factors and the intervention of 尾 -asarone in hippocampus of depression rats and to explore its related mechanism. Methods: chronic mild unpredictable stress stimulation (CUMS) rat model was established. 100 rats were randomly divided into 5 groups: normal group, model group, fluoxetine group (10 mg 路kg ~ (-1), 尾 -asarone group (25 mg 路kg ~ (-1) and high dose group (50 mg 路kg ~ (-1). From the 8th day, the rats were given orally once a day for 21 days. The open field experiment was carried out on day 0 and day 29, and the changes of Nissl bodies in hippocampal neurons were observed by Nissl staining. The expression of protein kinase R-like endoplasmic reticulum kinase (PERK) / enhancer protein homologue protein (CHOPN) and calcium reticulum protein (CRT) mRNA in hippocampal tissues of rats in each group were detected by real-time fluorescence quantitative PCR(Real-time. Western blotting technique was used to detect the CRT expression in rat hippocampal tissue. Results: after 28 days of chronic unpredictable mild stimulation, the scores of horizontal and vertical movements in the model group were significantly lower than those in the normal group, and the scores of 尾 -asarone were lower than those in the model group, while those in the high dose group and fluoxetine group were significantly lower than those in the model group. The scores of horizontal and vertical movements increased significantly (P 0.05). The results of Nissl staining showed that the cytoplasm of hippocampal neurons in the model group was shallower, and the granules of Nissl corpuscles were significantly decreased, while 尾 -asarone was low, and the morphology of neurons in the hippocampal area of the high dose group was relatively good, and the number of the granules in the hippocampal area of the model group was higher than that in the model group. Compared with the normal group, the expression of PERKG CHOPOCRT mRNA was up-regulated in the model group, and the expression of 尾 -asarone was lower in the model group than in the model group. The expression of PERKTCHOPOP-CRT mRNA in the high dose group and fluoxetine group was significantly down-regulated as compared with the model group, and the expression of P0.05T was down-regulated in the high dose group and fluoxetine group. Compared with the normal group, the expression of PERKG CHOPCRT protein in the model group was significantly higher than that in the model group, and in fluoxetine group, 尾 -asarone was lower than that in the high dose group, and the expression of PERK- CHOPP-CRT protein in the high dose group was significantly lower than that in the model group. Conclusion: 尾-asarone may play an antidepressant role by regulating the endoplasmic reticulum function in the hippocampus.
【作者單位】: 齊齊哈爾醫(yī)學(xué)院;
【基金】:黑龍江省科技廳攻關(guān)項目(PC13S06)
【分類號】:R285.5;R-332
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