本文選題：香蘭素 + 反向虛擬篩選　； 參考：《安徽醫(yī)科大學(xué)》2014年碩士論文

【摘要】：研究背景及目的 MDD的干預(yù)目前主要采用5-HT再攝取抑制劑（SSRI）等抗抑郁藥物。在肯定這些新型抗抑郁藥研究成果的同時(shí)，其療效、毒副作用及給藥途徑等依然需要研究者的繼續(xù)改進(jìn)。香蘭素分子具有奶香的氣息，是被廣泛使用的可食用香料。研究顯示香蘭素具有抗焦慮、抗菌、抗氧化等作用。自然界及人體內(nèi)香蘭素有哪些蛋白作用靶點(diǎn)？ 由于嗅覺(jué)通路與情感中樞杏仁核、海馬等有廣泛的纖維聯(lián)系，這成為嗅覺(jué)通路調(diào)節(jié)情感中樞的理論基礎(chǔ)，經(jīng)嗅覺(jué)通路對(duì)神經(jīng)系統(tǒng)進(jìn)行干預(yù)的報(bào)道也越來(lái)越多。嗅覺(jué)通的給藥途徑起效迅速、無(wú)外周毒、副作用、途徑方便。香蘭素分子“令人愉快”的氣味對(duì)MDD患者能否起到干預(yù)作用，，其機(jī)制是什么？ 本實(shí)驗(yàn)通過(guò)計(jì)算機(jī)反向虛擬篩選，探討香蘭素可能作用的蛋白晶體，并通過(guò)讓MDD大鼠吸嗅含香蘭素的氣霧劑，研究香蘭素吸嗅的抗抑郁作用及機(jī)制。 第一部分香蘭素分子藥用靶標(biāo)計(jì)算機(jī)反向虛擬篩選 藥物與蛋白質(zhì)分子（受體）的結(jié)合類似于鑰匙與鎖的識(shí)別關(guān)系。為了探討香蘭素可能作用的受體蛋白，利用分子對(duì)接軟件Surflex對(duì)sc-PDB蛋白數(shù)據(jù)庫(kù)進(jìn)行反向虛擬篩選，軟件對(duì)篩選結(jié)果進(jìn)行打分，打分結(jié)果大于8分的說(shuō)明與靶標(biāo)有較大的相關(guān)性，分值越高的蛋白與香蘭素分子的相關(guān)性也就越高，這種虛擬篩選為香蘭素的作用受體的研究及藥用價(jià)值的開(kāi)發(fā)提供了指導(dǎo)意義。 結(jié)果 篩選出來(lái)的大于8分的蛋白晶體為：羧乙基精氨酸β-內(nèi)酰胺酶、金屬β內(nèi)酰胺酶、結(jié)合分支桿菌水楊酸合成酶、β內(nèi)酰胺酶（IMP-1）。打分前20位的蛋白晶體見(jiàn)表3-1。篩選結(jié)果與香蘭素抗菌、抗氧化作用的報(bào)道基本一致。 第二部分MDD大鼠吸嗅香蘭素神經(jīng)行為學(xué)觀察 CUMS+孤養(yǎng)的方法建立大鼠MDD模型。根據(jù)干預(yù)的方式將建模成功后的大鼠分為：香蘭素吸嗅組、氟西汀灌胃組、純水吸嗅組，以及OBX+香蘭素吸嗅組和假手術(shù)組（Sham）。每組大鼠給予相應(yīng)的干預(yù)4w，觀察4w后各組大鼠糖水消耗量、強(qiáng)迫游泳不動(dòng)時(shí)間較干預(yù)前的變化。 結(jié)果 與干預(yù)前相比，干預(yù)4w后香蘭素吸嗅組和氟西汀灌胃組大鼠FST不動(dòng)時(shí)間、SCT糖水消耗有顯著性差異；純水吸嗅組和OBX+香蘭素吸嗅組未見(jiàn)顯著性差異。 第三部分香蘭素吸嗅對(duì)大鼠腦內(nèi)5-HT、DA、NE濃度的影響 神經(jīng)行為學(xué)的觀察結(jié)果顯示，香蘭素能經(jīng)嗅覺(jué)通路改善大鼠的抑郁樣行為。為了探索其作用機(jī)制，將大鼠麻醉處死后取腦，通過(guò)UPLC FLR （超高壓液相色譜 熒光檢測(cè)器）檢測(cè)各組大鼠腦勻漿液內(nèi)5 HT、 DA、 NE量，并通過(guò)蛋白試劑盒（BCA protein assay kits）檢測(cè)各組大鼠腦勻漿液可溶性蛋白含量（Pr）作為內(nèi)標(biāo)。 結(jié)果 香蘭素吸嗅組和氟西汀灌胃組大鼠腦勻漿液5-HT、DA的量顯著高于純水吸嗅組，而NE未見(jiàn)顯著性差異。OBX+香蘭素吸嗅組大鼠腦勻漿液5-HT、DA、NE均顯著低于Sham組。 結(jié)論 1香蘭素反向虛擬篩選的結(jié)果與其抑菌、抗氧化等報(bào)道一致 2香蘭素吸嗅能改善SD大鼠抑郁樣行為 3香蘭素抗抑郁作用可能是提升了腦5-HT、DA所實(shí)現(xiàn)
[Abstract]:Background and purpose of study

At the same time , the therapeutic effect , toxic side effect and administration route of the novel antidepressants still need to be improved by the investigator . The vanillin molecule has the flavor of milk fragrance and is widely used edible spice . The research shows that vanillin has anti - anxiety , antibacterial , anti - oxidation , etc . The research shows that the vanillin has anti - anxiety , antibacterial , anti - oxidation and the like .

The olfactory pathway has a wide range of fiber connections , such as almond kernel , hippocampus and so on , which is the theoretical basis of olfactory pathway regulating the emotion center . The olfactory pathway has more and more reports on the nervous system intervention . The olfactory pathway has rapid effect , no peripheral toxicity , side effect and convenient route . The pleasant smell of vanillin molecule can interfere with the patients with MDD . What is the mechanism ?

This experiment was carried out by computer reverse virtual screening to investigate the possible protein crystals of vanillin , and to study the antidepressant effect and mechanism of Vanillin ' s absorption and sniffing by inhalation of Vanillin - containing aerosol in MDD rats .

Reverse virtual screening of the first part of vanillin molecular medicine target computer

In order to explore the possible receptor protein of vanillin , a molecular docking software Surflex was used to reverse virtual screening of sc - PDB protein database .

Results

The screened protein crystals were carboxyethylarginine . beta . - lactamase , metal beta - lactamase , combined mycobacterial salicylic acid synthetase , beta - lactamase ( IMP - 1 ) . The protein crystals of the first 20 positions were shown in Table 3 - 1 . The screening results were consistent with the reported anti - bacterial and anti - oxidation effects of vanillin .

Neurobehavioral Observation of Olfactory Vanillin in the Second Part of MDD Rats

The rats were divided into three groups : vanillin inhalation group , fluoxetine group , pure water absorption and sniffing group , OBX + vanillin inhalation group and sham operation group ( Sham ) .

Results

Compared with the prior intervention , there was a significant difference in SCT sugar and water consumption after the intervention of 4w after 4w treatment of vanillin inhalation group and fluxitin irrigation group .
There was no significant difference in the sniffing group of pure water and OBX + Vanillin .

Effects of the third part of vanillin on the concentration of 5 - HT , DA and NE in rat brain

紲炵粡琛屼負(fù)瀛︾殑瑙傚療緇撴灉鏄劇ず,棣欏叞绱犺兘緇忓梾瑙夐

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