线虫作为痛风研究模式生物的评估研究

发布时间：2019-05-23 22:41

【摘要】：痛风是长期嘌呤代谢障碍、血尿酸增高引致组织损伤的一组疾病。随着人们生活水平的提高和饮食结构的改变，痛风的发病率逐年上升。痛风疾病的研究目前没有找到合适的模式生物，而秀丽隐杆线虫具有寿命短、繁殖快、饲养简单等特点，人类痛风相关基因在线虫中大部分都有对应，线虫可能是比较适合研究痛风的模型。本文通过文献查阅和信息收集，在线虫中找到了与人类痛风相关基因对应的同源基因，并利用KGML软件成功构建了线虫痛风局部基因网络。它可以清晰地展示出痛风相关基因、中间基因、小分子化合物和各种代谢途径之间的关联，，进而研究整个基因网络状态的变化，为探究痛风的发病机理提供了一个新平台。通过给线虫喂食三种不同浓度（0.1%、1%和10%）的7种贝类海鲜混合水提液，并观察在其生命周期内生理特征（寿命、活性和繁殖能力等）变化，发现喂食10%浓度混合海鲜水提液的线虫寿命较短、活性较低、繁殖能力较差，后期还出现了身体僵直的现象。随后采用10%浓度的七种单一贝类海鲜水提液分别培养线虫，发现10%浓度的文蛤和杂色蛤对线虫的影响最大。推测其原因可能是由于线虫进食了过量的富含嘌呤的海鲜，在体内过量积累，线虫代谢紊乱导致的。通过实时荧光定量PCR，分别对10%浓度文蛤和杂色蛤喂养5天、10天和15天线虫的痛风相关基因表达水平进行检测，发现各基因的表达量发生了不同的变化，可能对线虫痛风局部基因网络中各代谢途径（嘌呤代谢、糖代谢、TCA循环和氨基酸代谢等）产生影响，为痛风发病分子机制的研究提供参考。
[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.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R589.7;R-332

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