本文選題：精神分裂癥 + Ⅱ型糖尿病��； 參考：《華東師范大學》2013年碩士論文

【摘要】：精神分裂癥和Ⅱ型糖尿病均是復雜疾病。精神分裂癥是一種常見的精神病,其病因復雜,既有神經(jīng)生物學因素、遺傳學因素,也有社會心理學方面的因素,目前尚未完全闡明。此病多發(fā)病于青壯年,典型的癥狀有陽性癥狀和陰性癥狀之分,主要是指患者在感知、思維、情感、意志行為等多方面出現(xiàn)障礙,其精神活動與周圍環(huán)境和內(nèi)心體驗不協(xié)調(diào),脫離現(xiàn)實。病程多遷延,反復發(fā)作,部分患者發(fā)生精神活動衰竭和不同程度社會功能缺損。Ⅱ型糖尿病是一種代謝發(fā)生紊亂的疾病,其患者不需要依靠胰島素,可以使用口服降糖藥物來控制血糖,故又稱非胰島素依賴糖尿病。這種病也是在多種致病因素的作用下,經(jīng)過漫長的病理過程而形成的。其典型的癥狀為三多一少,即多尿、多飲、多食和消瘦。也有一些患者癥狀不典型,他們僅有頭昏、乏力等,甚至無癥狀。由于Ⅱ型糖尿病近來在兒童和青少年中的發(fā)病率迅速增加,己成為社會關(guān)注的問題。大量研究表明,精神分裂癥患者容易出現(xiàn)Ⅱ型糖尿病的癥狀,但兩者之間潛在的致病機制以及它們之間的關(guān)聯(lián)仍然不明確。在這篇文章中,我們基于通路分析和蛋白質(zhì)相互作用的方法探討了兩種病的發(fā)病機制以及它們之間的關(guān)聯(lián)。 本研究中首先利用精神分裂癥和Ⅱ型糖尿病的優(yōu)選易感基因集合,基于超幾何分布的統(tǒng)計分析方法富集到了一些分別對精神分裂癥和Ⅱ型糖尿病或者同時對這兩種疾病都有顯著意義的通路(校正后的p值0.05,p值校正采用的是Benj amini-Hochberg方法)。然后建立了一個顯著通路相互作用的網(wǎng)絡(luò)來探討它們之間的串擾。結(jié)果表明,通過某些易感基因,精神分裂癥和Ⅱ型糖尿病共享一些顯著通路。針對精神分裂癥和Ⅱ型糖尿病易感基因集中所有的382個易感基因,我們還利用了人類蛋白參考數(shù)據(jù)庫中的蛋白質(zhì)相互作用的數(shù)據(jù),從中提取出與這382個易感基因所編碼的蛋白和相互作用的那些蛋白質(zhì),將它們的相互作用關(guān)系重新建立了一個網(wǎng)絡(luò),并對網(wǎng)絡(luò)中那些degree比較高的蛋白進行了進一步的分析。其中有364個蛋白同時與精神分裂癥蛋白和Ⅱ型糖尿病蛋白有相互作用關(guān)系,這些蛋白被假定為這兩種病的新的致病因子。我們對這364個蛋白進行了系統(tǒng)的文獻挖掘,進一步驗證了它們與兩種病之間關(guān)聯(lián)的密切關(guān)系。此外,一些樞紐蛋白質(zhì)的具有高度的連通性,與兩種疾病中的多個易感蛋白均有相互作用,這意味著它們在兩種病的致病關(guān)聯(lián)中所起的多效性作用。有些樞紐蛋白是我們所富集到的通路的組成成分,包括鈣離子信號通路,g分泌酶介導的ErbB4信號通路,脂肪細胞因子信號通路,胰島素信號通路,AKT信號通路和Ⅱ型糖尿病通路。通過整合多方面的信息,我們假設(shè)那些同時包含有精神分裂癥和Ⅱ型糖尿病易感基因的信號通路為聯(lián)結(jié)這兩種疾病的重要通路。AKT可能是其中一個非常重要的共享組件并在兩種疾病的致病過程中發(fā)揮著關(guān)鍵的作用。 我們這項研究的創(chuàng)新點在于,基于通路分析和蛋白質(zhì)相互作用的方法來研究這兩種疾病的致病機理以及它們之間的關(guān)聯(lián),這是第一次。并且,我們探索出一些可能對兩種疾病的關(guān)聯(lián)起重要作用的候選基因。這項研究為科研人員提供了關(guān)于兩種疾病的共致病性關(guān)聯(lián)的新見解,同時,也促進了共致病新模型的提出。而且在兩種疾病共享的顯著性通路中發(fā)揮多效性作用的一些病原學因子可能對疾病有重要的影響,更有可能成為治療干預的目標,文章中的這一觀點對藥物研發(fā)人員發(fā)現(xiàn)新的藥物靶點也有一些啟發(fā)。
[Abstract]:Schizophrenia and type II diabetes are complex diseases. Schizophrenia is a common psychosis with complex causes, including neurobiological, genetic and social psychological factors. It is not fully elucidated at present. This disease is frequently occurring in young and young adults, with typical symptoms and negative symptoms. It mainly refers to the disorder in many aspects, such as perception, thinking, emotion, and will behavior. The mental activity is incompatible with the surrounding environment and inner experience. It is divorced from reality. The course of the disease is more deferred, repeated episodes, some patients have mental exhaustion and different degrees of social function defects. Type II diabetes is a metabolic disorder, The patient does not need to rely on insulin and can use oral hypoglycemic drugs to control blood sugar, so it is also called non insulin dependence on diabetes. This disease is also formed in a long period of pathological process under the action of various pathogenic factors. Its typical symptoms are more than three, that is polyuria, polydipsia, polydipsia and emaciation. There are also some patients' symptoms. Atypical, they are only dizzy, tired, and even asymptomatic. Since type II diabetes has recently increased rapidly in children and adolescents, it has become a social concern. A large number of studies have shown that schizophrenia patients are prone to the symptoms of type 2 diabetes, but the underlying pathogenesis and the relationship between them and their relationship are between them. In this article, we explored the pathogenesis and the association between the two diseases based on the pathway analysis and protein interaction.
In this study, we first made use of the preferred susceptibility gene set of schizophrenia and type 2 diabetes. Based on the hypergeometric distribution, some pathways were enriched for schizophrenia, type II diabetes, or both of these two diseases (corrected P 0.05, and P value correction using Benj amini-). The Hochberg method. Then a network of significant pathway interaction was established to explore the crosstalk between them. The results showed that some significant pathways were shared by some susceptible genes, schizophrenia and type II diabetes. We also used 382 susceptible genes for schizophrenia and type II diabetes susceptibility genes to concentrate all the susceptible genes. The protein interaction data in the human protein reference database, extracted from the proteins encoded by the 382 susceptible genes and the proteins interacting with them, reestablished a network of their interactions and further analyzed the higher degree proteins in the network. 3 of them were further analyzed. The 64 proteins interact with schizophrenia protein and type II diabetes protein, which are assumed to be new pathogenic factors of the two diseases. We systematically document these 364 proteins and further verify the close relationship between them and two diseases. There is a high degree of connectivity that interacts with multiple susceptible proteins of two diseases, which means their pleiotropic action in the pathogenetic Association of two diseases. Some hinge proteins are components of the pathway we enrich, including the calcium signaling pathway, the G secreted ErbB4 signaling pathway, and the adipocyte cause. Subsignaling pathways, insulin signaling pathways, AKT signaling pathways, and type II diabetes pathways. By integrating multiple information, we hypothesize that those signaling pathways that simultaneously contain schizophrenia and type II diabetes susceptibility genes are an important pathway to link these two diseases,.AKT, to be one of the most important shared components. The two diseases play a key role in the pathogenesis.
The innovation of our study is that it is the first time to study the pathogenesis and association of these two diseases based on pathway analysis and protein interaction, and we have explored some candidate genes that may play an important role in the association of the two diseases. New insights into the co pathogenicity of the two diseases also promote the presentation of a new co pathogenic model. Moreover, some etiological factors that play an effective role in the saliency pathways shared by the two diseases may have an important impact on the disease and are more likely to be the target of treatment intervention. The discovery of new drug targets also has some implications.
【學位授予單位】：華東師范大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R749.3;R587.1

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