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線蟲作為痛風研究模式生物的評估研究

發(fā)布時間:2019-05-23 22:41
【摘要】:痛風是長期嘌呤代謝障礙、血尿酸增高引致組織損傷的一組疾病。隨著人們生活水平的提高和飲食結(jié)構(gòu)的改變,痛風的發(fā)病率逐年上升。痛風疾病的研究目前沒有找到合適的模式生物,而秀麗隱桿線蟲具有壽命短、繁殖快、飼養(yǎng)簡單等特點,人類痛風相關(guān)基因在線蟲中大部分都有對應(yīng),線蟲可能是比較適合研究痛風的模型。 本文通過文獻查閱和信息收集,在線蟲中找到了與人類痛風相關(guān)基因?qū)?yīng)的同源基因,并利用KGML軟件成功構(gòu)建了線蟲痛風局部基因網(wǎng)絡(luò)。它可以清晰地展示出痛風相關(guān)基因、中間基因、小分子化合物和各種代謝途徑之間的關(guān)聯(lián),,進而研究整個基因網(wǎng)絡(luò)狀態(tài)的變化,為探究痛風的發(fā)病機理提供了一個新平臺。 通過給線蟲喂食三種不同濃度(0.1%、1%和10%)的7種貝類海鮮混合水提液,并觀察在其生命周期內(nèi)生理特征(壽命、活性和繁殖能力等)變化,發(fā)現(xiàn)喂食10%濃度混合海鮮水提液的線蟲壽命較短、活性較低、繁殖能力較差,后期還出現(xiàn)了身體僵直的現(xiàn)象。隨后采用10%濃度的七種單一貝類海鮮水提液分別培養(yǎng)線蟲,發(fā)現(xiàn)10%濃度的文蛤和雜色蛤?qū)蟲的影響最大。推測其原因可能是由于線蟲進食了過量的富含嘌呤的海鮮,在體內(nèi)過量積累,線蟲代謝紊亂導(dǎo)致的。 通過實時熒光定量PCR,分別對10%濃度文蛤和雜色蛤喂養(yǎng)5天、10天和15天線蟲的痛風相關(guān)基因表達水平進行檢測,發(fā)現(xiàn)各基因的表達量發(fā)生了不同的變化,可能對線蟲痛風局部基因網(wǎng)絡(luò)中各代謝途徑(嘌呤代謝、糖代謝、TCA循環(huán)和氨基酸代謝等)產(chǎn)生影響,為痛風發(fā)病分子機制的研究提供參考。
[Abstract]:Gout is a group of diseases caused by long-term purine metabolism disorder and high serum uric acid. With the improvement of people's living standards and the change of diet structure, the incidence of gout is increasing year by year. At present, no suitable model organism has been found in the study of gout disease, but Cryptococcus elegans has the characteristics of short life span, fast reproduction and simple feeding. Most of the genes related to human gout are corresponding in nematodes. Nematodes may be a more suitable model for the study of gout. In this paper, the homologous genes corresponding to human gout related genes were found in nematodes through literature review and information collection, and the local gene network of nematode gout was successfully constructed by using KGML software. It can clearly show the relationship between gout related genes, intermediate genes, small molecular compounds and various metabolic pathways, and then study the changes of the whole gene network state, which provides a new platform for exploring the pathogenesis of gout. Three different concentrations (0.1%, 1% and 10%) of seven shellfish seafood mixtures were fed to nematodes, and the changes of physiological characteristics (life span, activity and reproductive ability, etc.) were observed during their life cycle. It was found that the nematodes fed 10% mixed seafood water extract had short life span, low activity and poor reproductive ability, and the body was stiff in the later stage. Then seven kinds of single shellfish seafood water extract with 10% concentration were used to culture nematodes respectively. it was found that 10% concentration of Meretrix and Meretrix had the greatest effect on nematodes. It is speculated that the reason may be that nematodes eat too much purine-rich seafood, accumulate too much in the body, and cause metabolic disorder of nematodes. The expression levels of gout related genes in 10% concentration Meretrix and Meretrix were detected by real-time fluorescence quantitative PCR, (real-time fluorescence quantitative PCR,). It was found that the expression of gout related genes changed differently in 10% concentration Meretrix and Meretrix. It may have an effect on the metabolic pathways (purine metabolism, glucose metabolism, TCA cycle and amino acid metabolism, etc.) in the local gene network of nematode gout, which provides a reference for the study of the molecular mechanism of gout.
【學(xué)位授予單位】:哈爾濱工業(yè)大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2012
【分類號】:R589.7;R-332

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