基于iTRAQ技術的卒中后抑郁癥患者血漿蛋白質組學研究
發(fā)布時間:2018-05-29 20:39
本文選題:卒中后抑郁癥 + 中風 ; 參考:《重慶醫(yī)科大學》2014年碩士論文
【摘要】:研究背景 腦卒中后抑郁是腦卒中患者中最常見的精神疾病并發(fā)癥。卒中后抑郁可以影響到患者腦卒中的治療效果,加重身體殘疾,干擾患者的肢體功能恢復,增加患者的痛苦,甚至使患者產(chǎn)生自殺觀念。但是,目前卒中后抑郁疾病發(fā)生發(fā)展?jié)撛诘牟±砩頇C制尚不清楚,在臨床上也沒有可用于疾病診斷或病情監(jiān)測的檢測方法。 目的 本研究旨在運用蛋白質組學技術探討卒中后抑郁疾病患者血漿蛋白質組的變化,擬尋找卒中后抑郁患者血漿中異常表達的蛋白質,以期作為客觀診斷卒中后抑郁癥的生物標志物,從而為疾病的診斷、預防、發(fā)病機制及治療提供依據(jù)。 方法 本研究是對卒中后抑郁組(15例)、卒中組(15例)和正常對照組(15例)受試者的血漿蛋白質進行的一個比較蛋白質組學研究。首先對三組受試者的血漿進行14種高豐度蛋白的去除,,然后采用iTRAQ同位素標記與多維液相色譜分離串聯(lián)質譜技術對三組受試者的樣本進行相對定量分析和質譜鑒定,最后通過免疫印跡法對蛋白質組學結果進行進一步驗證,并對顯著改變的差異蛋白搜索數(shù)據(jù)庫進行生物信息分析。 結果 蛋白質組學研究結果顯示蛋白表達量顯著改變的蛋白質的生物學功能主要與脂質代謝和免疫調節(jié)有關,我們選擇了與這些生物功能密切相關的6個蛋白(ApoA-IV,ApoC-II,CRP,gelsolin,haptoglobin,LRG)進行了Western blotting驗證。與卒中組比較,蛋白ApoA-IV的表達量在卒中后抑郁中顯著上調,ApoC-II、 LRG和CRP三個蛋白的表達量在卒中后抑郁組和正常對照組中顯著下調。而gelsolin和haptoglobin這兩個蛋白的表達量在三組中都有顯著地改變(gelsolin:正常對照組卒中后抑郁組卒中組;haptoglobin,卒中組卒中后抑郁組正常對照組)。 結論 由于gelsolin和haptoglobin這兩個蛋白顯示出獨特的蛋白分層表達譜,所以gelsolin蛋白表達量的提高聯(lián)合haptoglobin蛋白表達量的降低可能可以作為臨床上卒中患者產(chǎn)生抑郁癥狀風險增加的診斷標志物
[Abstract]:Research background Post-stroke depression is the most common complication of mental illness in stroke patients. Post-stroke depression can affect the therapeutic effect of stroke, aggravate the body disability, interfere with the recovery of limb function, increase the pain of patients, and even lead to suicidal concept. However, the underlying pathophysiological mechanism of post-stroke depression is not clear, and there is no clinical detection method for disease diagnosis or disease monitoring. Purpose The aim of this study was to investigate the changes of plasma proteome in patients with post-stroke depression by using proteomics techniques, and to seek abnormal expression of proteins in plasma of patients with post-stroke depression. It is expected to be used as a biomarker for the objective diagnosis of post-stroke depression and to provide evidence for the diagnosis, prevention, pathogenesis and treatment of the disease. Method This study was a comparative proteomic study of plasma proteins in 15 patients with post-stroke depression, 15 patients with stroke and 15 normal controls. At first, 14 kinds of high abundance proteins were removed from the plasma of the three groups, and then the samples of the three groups were analyzed quantitatively by iTRAQ isotope labeling and tandem mass spectrometry with multi-dimensional liquid chromatography. Finally, the proteomics results were further verified by Western blotting, and the significant change of differential protein search database was analyzed by bioinformatics. Result The results of proteomics showed that the biological functions of proteins with significant changes in protein expression were mainly related to lipid metabolism and immunomodulation. We selected six proteins, ApoA-IVApoC-II, CRPgelsolinhaptoglobinine (LRGG), which were closely related to these biological functions, to be verified by Western blotting. Compared with stroke group, the expression of protein ApoA-IV significantly up-regulated the expression of ApoC-II, LRG and CRP in post-stroke depression group and normal control group. However, the expression of gelsolin and haptoglobin were significantly changed in the three groups: normal control group, post-stroke depression group, stroke group, normal control group. Conclusion Because the two proteins gelsolin and haptoglobin show unique protein layering expression profile, the increase of gelsolin protein expression combined with the decrease of haptoglobin protein expression may be used as a diagnostic marker for the increased risk of depression in patients with stroke.
【學位授予單位】:重慶醫(yī)科大學
【學位級別】:碩士
【學位授予年份】:2014
【分類號】:R743.3;R749.4
【參考文獻】
相關期刊論文 前1條
1 王玉果;;腦卒中偏癱136例的早期護理干預[J];中國誤診學雜志;2010年35期
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