本文選題：HIV + 口腔��； 參考：《昆明醫(yī)科大學(xué)》2017年碩士論文

【摘要】：[目的]口腔對(duì)于HIV感染的認(rèn)識(shí)具有重要作用,但因HIV引起的口腔環(huán)境改變和口腔病變的發(fā)病機(jī)制仍不清楚�？谇粌�(nèi)的代謝產(chǎn)物主要由宿主和微生物產(chǎn)生,分析口腔代謝物特性,將有助于進(jìn)一步探明HIV感染相關(guān)口腔疾病發(fā)病機(jī)制及發(fā)現(xiàn)新的疾病狀態(tài)的診斷靶標(biāo)。目前,僅國外有少量關(guān)于HIV感染口腔代謝產(chǎn)物變化的報(bào)道,國內(nèi)尚未開展此領(lǐng)域的研究。本研究擬采用病例對(duì)照設(shè)計(jì)方案,以及高通量的液相色譜-質(zhì)譜(LC-MS)聯(lián)用和氣相色譜-質(zhì)譜(GC-MS)聯(lián)用代謝組學(xué)技術(shù),比較健康人群和HIV感染者的口腔代謝物變化,旨在初步探明HIV相關(guān)口腔代謝物改變特征,以期為HIV感染早期診斷、病情監(jiān)測(cè)和治療尋找新的潛在的生物標(biāo)志物。[方法]擬收集未接受HAART的30例HIV陽性感染者和對(duì)照組30例HIV陰性受試者的口腔液標(biāo)本。分別采用氣相色譜-質(zhì)譜聯(lián)用和液相色譜-質(zhì)譜聯(lián)用方法對(duì)全部口腔液樣本進(jìn)行檢測(cè)及生物信息學(xué)分析,最后篩選出有意義的差異代謝物。[結(jié)果]30名HIV感染者的CD4+淋巴計(jì)數(shù)分布在13. 9-200個(gè)/μL之間。通過這兩種代謝組學(xué)方法檢測(cè)后,先經(jīng)PCA分析,都證實(shí)所有樣本主成分相似;再經(jīng)OPLS-DA分析,證實(shí)HIV感染者組的口腔代謝有變化。經(jīng)過篩選經(jīng)GC-MS檢測(cè)發(fā)現(xiàn)了十種代謝差異物,其中病例組口腔液葡萄糖、檸檬酸、磷酸鹽、D-塔羅糖、半乳糖、赤酮酸內(nèi)酯和α-氨基己二酸水平升高,而丙二胺、甲氧基吲哚和丁酮酸含量降低;在LC-MS檢測(cè)中發(fā)現(xiàn)了九種代謝差異物,其中病例組口腔液膽堿、L-瓜氨酸、黃嘌呤、2-脫氧核苷、胸苷、磷酰膽堿、絲氨酸-亮氨酸小肽水平升高,而3-羥基-3-甲基戊二酸和L-古洛糖酸γ-內(nèi)酯水平降低。以這些代謝物質(zhì)為依據(jù),通過KEGG分析,在GC-MS檢測(cè)中發(fā)現(xiàn)碳水化合物代謝途徑和氨基酸代謝途徑有變化,而在LC-MS檢測(cè)中發(fā)現(xiàn)氨基酸代謝途徑、脂質(zhì)代謝途徑和核苷酸代謝途徑受到了影響。最后通過代謝通路分析,在GC-MS檢測(cè)中發(fā)現(xiàn)檸檬酸循環(huán)、磷酸鹽代謝、纈氨酸、亮氨酸和異亮氨酸的生物合成、賴氨酸的生物合成及β丙氨酸代謝可能受到了影響;LC-MS檢測(cè)中發(fā)現(xiàn)咖啡因代謝、甘油磷脂代謝、精氨酸和脯氨酸代謝、嘌呤代謝和嘧啶代謝可能受到了影響。[結(jié)論]用代謝組學(xué)方法證實(shí)了 HIV感染者的口腔液代謝變化明顯,并不能用某一種單一的異常代謝標(biāo)記物來診斷疾病,但是可以用一組口腔生物標(biāo)記物反映患者體內(nèi)代謝變化的輪廓。并且,采用不同的代謝組學(xué)方法進(jìn)行研究可以提供更全面的代謝生物學(xué)信息。
[Abstract]:Objective: oral cavity plays an important role in the recognition of HIV infection, but the changes of oral environment and the pathogenesis of oral lesions caused by HIV are still unclear. The metabolites in oral cavity are mainly produced by host and microorganism. Analyzing the characteristics of oral metabolites will be helpful to further study the pathogenesis of oral diseases associated with HIV infection and to find new diagnostic targets of disease status. At present, there are only a few reports about the changes of oral metabolites of HIV infection in foreign countries, but no research in this field has been carried out in China. In this study, a case-control design and high throughput liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) metabolic techniques were used to compare the changes of oral metabolites between healthy people and those infected with HIV. The purpose of this study was to identify the characteristics of oral metabolites related to HIV and to find new potential biomarkers for the early diagnosis, disease monitoring and treatment of HIV infection. [methods] Oral fluid samples of 30 HIV positive patients without HAART and 30 HIV negative controls were collected. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to detect and bioinformatics of all oral liquid samples. [results] the distribution of CD4 lymphatic count in 30 patients with HIV infection was 13.3%. Between 9-200 / 渭 L. After the detection of these two methods, PCA analysis confirmed that all the main components of the samples were similar, and the oral metabolism of HIV infected patients was confirmed by OPLS-DA analysis. Ten metabolic differences were found by screening and GC-MS analysis. The oral fluid glucose, citric acid, phosphate D-taroose, galactose, klycolactone and 偽 -aminoadipic acid increased in the case group, while the level of propanediamine was increased in the case group. The contents of methoxyindole and butanoic acid decreased, nine metabolites were found in LC-MS test, among them, the levels of choline L-citrulline, xanthine 2-deoxynucleoside, thymidine, phosphorylcholine, serine leucine small peptide increased in the case group. However, the levels of 3-hydroxyl-3-methyl glutaric acid and L-glutaric acid 緯-lactone decreased. Based on these metabolites and KEGG analysis, carbohydrate metabolic pathway and amino acid metabolic pathway were found in GC-MS detection, while amino acid metabolic pathway was found in LC-MS assay. Lipid metabolism pathway and nucleotide metabolism pathway are affected. Finally, the citric acid cycle, phosphate metabolism, valine, leucine and isoleucine biosynthesis were found in GC-MS analysis. The biosynthesis of lysine and 尾 -alanine metabolism may be affected by LC-MS. Caffeine metabolism, glycerol phospholipid metabolism, arginine and proline metabolism, purine metabolism and pyrimidine metabolism may be affected. [conclusion] the metabolic changes in oral fluid of HIV infected patients were confirmed by the method of metabonomics, and no single abnormal metabolic marker could be used to diagnose the disease. However, a set of oral biomarkers can be used to reflect the profile of metabolic changes in patients. Moreover, using different metabonomics methods can provide more comprehensive information about metabolic biology.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R512.91;R781.6

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