本文關(guān)鍵詞： 丙型肝炎病毒自發(fā)清除 丙型肝炎慢性感染 血清代謝組學(xué) 液相色譜-串聯(lián)質(zhì)譜聯(lián)用（LC-MS/MS） 主成分分析（PCA） 正交偏最小二乘法-判別分析（OPLS-DA）　出處：《吉林大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：丙型肝炎是一種嚴(yán)重威脅全球公共健康的疾病，目前尚無有效疫苗可預(yù)防。據(jù)估計(jì)全世界范圍內(nèi)約有1.8億人感染HCV，主要通過輸血和血制品、破損的皮膚和黏膜等途徑傳播。HCV急性感染者中約有20%～30%可實(shí)現(xiàn)病毒自發(fā)清除，感染HCV6個月后病毒仍未清除稱為慢性丙型肝炎，約50%～80%的HCV感染者將進(jìn)展為慢性感染狀態(tài)，其中20%～30%的患者將發(fā)展為肝硬化或肝癌。目前丙肝的標(biāo)準(zhǔn)治療方法為聚乙二醇干擾素聯(lián)合利巴韋林(PEG-IFN-α/RBV)治療，由于療程長、不良反應(yīng)大、IFN價格相對較高和持續(xù)病毒學(xué)應(yīng)答率較低等原因，給患者治療帶來較大負(fù)擔(dān)。 代謝組學(xué)研究源于代謝輪廓分析（metabolic profiling），作為一個新的研究手段，已成為系統(tǒng)生物學(xué)的重要組成部分，主要反映在外界刺激下由于組織細(xì)胞的病理生理學(xué)改變而引起的代謝產(chǎn)物相應(yīng)改變。代謝組學(xué)多以相對分子量小于1000Da的內(nèi)源性代謝產(chǎn)物為研究對象，，可從整體上發(fā)現(xiàn)生物樣本代謝組分的改變。目前在疾病診斷與治療、新藥研制開發(fā)、藥物作用和毒性機(jī)制研究等方面已顯示出較明顯優(yōu)勢。 本研究納入了丙型肝炎病毒自發(fā)清除組、慢性丙型肝炎組和健康對照組各30例樣本作為研究對象，采用快速液相色譜-串聯(lián)質(zhì)譜聯(lián)用（LC-MS/MS）技術(shù)，應(yīng)用主成分分析（PCA）、正交偏最小二乘法-判別分析（OPLS-DA）進(jìn)行模式識別，然后通過變量重要性因子（VIP）、非參數(shù)檢驗(yàn)，結(jié)合數(shù)據(jù)庫檢索篩選鑒定出慢性丙型肝炎組、健康對照組及丙型肝炎病毒自發(fā)清除組間差異的代謝物。 研究共發(fā)現(xiàn)25種代謝物在以上三組中存在顯著差異，其中7個變量被鑒定為花生四烯酸、棕櫚油酸、葵�；鈮A、溶血磷脂酰膽堿（20:5,16:0）、溶血磷脂酰乙醇胺（16:0,18:0），涉及脂肪酸、磷脂等代謝。其中花生四烯酸以及未鑒定出明確結(jié)構(gòu)的m/z179.0719、m/z382.1360、m/z548.3475、m/z680.4281、m/z303.2323等物質(zhì)與丙型肝炎病毒自發(fā)清除組的相關(guān)性較好，受試者工作特征曲線（ROC）下面積為0.887~0.977，具有較好的特異性和敏感性。 丙型肝炎病毒自發(fā)清除組、慢性丙型肝炎組和健康對照組在血清代謝水平上存在較明顯差異，這些差異物可能與丙型肝炎病毒感染后出現(xiàn)的不同臨床轉(zhuǎn)歸有關(guān)。
[Abstract]:Hepatitis C is a serious threat to global public health, and there is no effective vaccine to prevent it. It is estimated that about 180 million people worldwide are infected with HCV, mainly through blood transfusions and blood products. About 20% of the acute infected people with HCV6 can realize the spontaneous clearance of the virus, and the virus has not been cleared of chronic hepatitis C for months after infection with HCV6. About 50% of HCV infected people will progress to chronic infection. Twenty percent of the patients will develop cirrhosis or liver cancer. The current standard treatment for hepatitis C is PEG-IFN- 偽 / RBV combined with pebavirin. Because of the long course of treatment, the high price of IFNs and the low rate of persistent virological response, the treatment of IFNs brings a great burden to the patients. Metabonomics, as a new research tool, has become an important part of system biology because it originated from metabolic profile analysis. It is mainly reflected in the corresponding changes of metabolites caused by pathophysiological changes of histocytes under external stimulation. Metabolites with relative molecular weight less than 1000Da are the research objects. The changes of metabolic components in biological samples can be found as a whole. At present, there are obvious advantages in the diagnosis and treatment of diseases, the development of new drugs, the study of drug action and the mechanism of toxicity, etc. In this study, 30 samples of hepatitis C virus spontaneous clearance group, 30 cases of chronic hepatitis C group and 30 healthy control group were included as the study objects. A rapid liquid chromatography-tandem mass spectrometry (LC-MS / MS) technique was used to identify the patterns by using principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA). Then the metabolites of chronic hepatitis C group, healthy control group and hepatitis C virus spontaneous clearance group were identified by variable importance factor (VIPP), nonparametric test and database retrieval. A total of 25 metabolites were identified as arachidonic acid, palmitic oil acid, sunacylcarnitine and lysophosphatidylcholine 20: 5, among which 7 variables were identified as arachidonic acid, palmitic oil acid and lysophosphatidylcholine 20: 5. 16: 0, lysophosphatidyl ethanolamine 16: 0 0: 0, involved in fatty acid, phospholipid metabolism, among them arachidonic acid and mrz179.0719, whose structure has not been identified. M / z 382.1360 m / m / z 548.3475N / m / z 680.4281m / z 303.2323 and so on, have a good correlation with the group of spontaneous clearance of hepatitis C virus. The area under the operating characteristic curve (ROC) is 0. 887 ~ 0. 977, which has good specificity and sensitivity. There were significant differences in serum metabolic level among the spontaneous clearance group of hepatitis C virus, chronic hepatitis C group and healthy control group. These differences may be related to different clinical outcomes after hepatitis C virus infection.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R512.63

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