本文選題：急性淋巴細(xì)胞白血病 + 表面激光解吸電離飛行時(shí)間質(zhì)譜��； 參考：《瀘州醫(yī)學(xué)院》2013年碩士論文

【摘要】：目的急性淋巴細(xì)胞白血病（ALL）是兒童時(shí)期最常見的血液系統(tǒng)腫瘤，出血是常見癥狀及死因之一，引起出血的機(jī)制復(fù)雜，其中最主要原因是血小板減少。ALL患兒血小板數(shù)量減少的同時(shí)，可能存在其功能異常。目前關(guān)于ALL患兒血小板功能的研究較少，其對(duì)出血影響的機(jī)制尚不完全清楚。本實(shí)驗(yàn)旨在應(yīng)用血小板蛋白質(zhì)組學(xué)技術(shù)分析兒童ALL狀態(tài)下血小板蛋白質(zhì)差異表達(dá)，并對(duì)這些差異表達(dá)蛋白質(zhì)進(jìn)行進(jìn)一步的研究和篩選，以期尋找到ALL患兒血小板功能相關(guān)的血小板特異性蛋白質(zhì)，探討ALL時(shí)血小板功能異常的分子機(jī)制，以便早期采取積極措施干預(yù)ALL患者的出血，從而改善預(yù)后。方法應(yīng)用蛋白質(zhì)芯片CM10及表面激光解吸電離飛行時(shí)間質(zhì)譜技術(shù)（SELDI-TOF-MS）技術(shù)獲得ALL患兒27例（ALL組）、ALL誘導(dǎo)緩解治療達(dá)到完全緩解患兒25例（ALL-CR1組）及正常對(duì)照組27例的整套血小板蛋白質(zhì)譜，采用Ciphergen公司Biomarker Wizard和BiomarkerPattern System5.0軟件對(duì)蛋白質(zhì)譜進(jìn)行差異蛋白分析，篩選出有顯著差異的蛋白質(zhì)。結(jié)果(1)在質(zhì)荷比2000～20000范圍內(nèi)，ALL組與正常對(duì)照組比較血小板質(zhì)譜中有176個(gè)差異表達(dá)的蛋白質(zhì)峰（p＜0.05），高表達(dá)有25個(gè)，低表達(dá)有151個(gè)。其中存在穩(wěn)定表達(dá)且變異系數(shù)小的蛋白質(zhì)峰有9個(gè)：包括高表達(dá)2個(gè)，荷質(zhì)比（M/Z）分別為2496.9和4287.9；低表達(dá)7個(gè)，荷質(zhì)比（M/Z）分別為7881.2、4091.3、3149.9、2365.1、9414.1、5252.3、2280.7。(2)ALL組與ALL-CR1組比較血小板質(zhì)譜中有112個(gè)差異表達(dá)的蛋白質(zhì)峰（p＜0.05），其中高表達(dá)有15個(gè)，低表達(dá)有97個(gè)，存在穩(wěn)定表達(dá)且變異系數(shù)小的蛋白質(zhì)峰有6個(gè)：包括高表達(dá)2個(gè)，荷質(zhì)比（M/Z）分別為2496.9和4287.9；低表達(dá)4個(gè)，荷質(zhì)比（M/Z）分別為9414.1、7881.2、3149.9、2280.7。(3)ALL-CR1組與正常對(duì)照組比較，未出現(xiàn)具有統(tǒng)計(jì)學(xué)意義的高表達(dá)蛋白質(zhì)峰（p＞0.05），但仍有69個(gè)顯著低表達(dá)的蛋白質(zhì)峰（p＜0.05）。(4)數(shù)據(jù)庫分析ALL組與正常對(duì)照組顯著差異的9個(gè)蛋白質(zhì)峰，表達(dá)上調(diào)的兩種蛋白分別為內(nèi)皮素-1和大內(nèi)皮素-1，，表達(dá)下調(diào)的蛋白為血小板第四因子、凝血酶輕鏈、垂體腺苷酸環(huán)化酶多肽27、纖維蛋白原β鏈和三種未知蛋白，這些蛋白質(zhì)可能與血小板信號(hào)轉(zhuǎn)導(dǎo)、粘附、聚集及活化等功能相關(guān)。結(jié)論(1) ALL患兒與正常對(duì)照組外周血血小板蛋白質(zhì)組學(xué)水平有顯著差異；(2)ALL組與ALL-CR1組間血小板蛋白質(zhì)組學(xué)水平也存在顯著差異，經(jīng)誘導(dǎo)緩解治療達(dá)完全緩解后異常表達(dá)的蛋白數(shù)目明顯減少，但與正常比較仍有一部分蛋白呈顯著低表達(dá)。(3)ALL患兒血小板功能可能存在異常，主要表現(xiàn)為細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)障礙、聚集和活化能力降低及凝血功能異常等方面；(4)本研究為ALL發(fā)病及治療過程中血小板功能的監(jiān)測(cè)提供了新途徑。
[Abstract]:Objective Acute lymphoblastic leukemia (ALL) is the most common hematological tumor in childhood. Hemorrhage is one of the common symptoms and causes of death. The main reason is that the number of thrombocytopenia. All may have abnormal function at the same time. At present, there are few studies on platelet function in children with ALL, and the mechanism of its effect on bleeding is not fully understood. The purpose of this study was to analyze the differential expression of platelet proteins in children with ALL by using platelet proteomics, and to further study and screen these differentially expressed proteins. The aim of this study was to find platelet specific proteins related to platelet function in children with ALL and to explore the molecular mechanism of platelet dysfunction in patients with ALL so as to take active measures to intervene the bleeding in patients with ALL early and improve the prognosis. Methods using CM10 and surface laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) technique, the complete set of 27 cases of ALL children in all group (25 cases of complete remission group) and 27 cases of normal control group (control group) were obtained by means of protein chip CM10 and surface laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS). Platelet protein profile, Biomarker Wizard and BiomarkerPattern System5.0 software of Ciphergen Company were used to analyze the differential protein profiles and the proteins with significant difference were screened out. Results 1) there were 176 differentially expressed protein peaks (p < 0.05), 25 high expression and 151 low expression in all group compared with normal control group within the range of 2000 ~ 2000.The results showed that there were 176 differentially expressed protein peaks (p < 0.05), 25 high expression and 151 low expression in all group as compared with those in normal control group. Among them, there are 9 protein peaks with stable expression and low coefficient of variation, including 2 high expression, 2496.9 and 4287.9, respectively, and 7 low expression. Compared with ALL-CR1 group, there were 112 differentially expressed protein peaks (p < 0.05) in platelets mass spectrometry (P < 0.05), 15 of which were overexpression and 97 were low expression, compared with the ALL-CR1 group, the ratio of charge to substance was 7881.2% 4091.3N 3149.9N 2365.1N 9414.1n 5252.3N 2280.7.2L all group, compared with ALL-CR1 group, there were 112 differentially expressed protein peaks (p < 0.05), among which 15 had high expression and 97 had low expression. There were 6 protein peaks with stable expression and low coefficient of variation, including 2 high expression, M / Z = 2496.9 and 4287.9, respectively, and 4 low expression, respectively. The ratio of M / Z and M / Z were 9414.1 / 7881.23149.9and 2280.7.3ALL-CR1, respectively, compared with the control group. There were no statistically significant high expression protein peaks (p > 0.05), but there were still 69 significant low expression protein peaks (p < 0.05, P < 0.05) in the ALL group and the control group, which were significantly different from those in the control group (P < 0.05), but there were still 69 protein peaks with significant differences between the ALL group and the normal control group. The up-regulated proteins were endothelin-1 and large endothelin-1. The down-regulated proteins were platelet fourth factor, thrombin light chain, pituitary adenylate cyclase polypeptide 27, fibrinogen 尾 chain and three unknown proteins. These proteins may be related to platelet signal transduction, adhesion, aggregation and activation. Conclusion (1) there is a significant difference in the level of platelet proteomics between children with ALL and normal controls. There is also a significant difference in the level of platelet proteomics between all group and ALL-CR1 group. The number of abnormally expressed proteins after induction remission therapy was significantly decreased, but some of the proteins were significantly lower than those of normal children. The platelet function of all children may be abnormal, mainly manifested as cell signal transduction disorder. This study provides a new approach for monitoring platelet function in the pathogenesis and treatment of ALL.
【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R733.71

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